Cancer Cell International最新文献

{"title":"The controversial role of CD151 in different solid tumors: promoter or suppressor?","authors":"Xue Gao, Sa Liu, Yubo Cao, Lei Shi, Yuanqin Yin","doi":"10.1186/s12935-025-03751-9","DOIUrl":"10.1186/s12935-025-03751-9","url":null,"abstract":"<p><p>As a member of the tetraspanin superfamily, CD151 plays a pivotal role in tumorigenesis, progression, and metastasis. CD151 is involved in various cellular processes, including cell-cell junction, signal transduction, epithelial-mesenchymal transition (EMT), cancer stem cell maintenance (CSCs), angiogenesis, and exosome regulation. Therefore, CD151 is a potential target for tumor therapy and may be valuable in tumor diagnosis and prognosis. Notably, while CD151 predominantly functions as an oncogene in most cancers, it can also exhibit tumor-suppressive roles in specific contexts, indicating that its function is context-dependent. Additionally, CD151 plays a significant role in modulating the immune microenvironment. For instance, CD151 supports the proliferation, activation, and migration of T cells. The CD151 peptide may function as a tumor vaccination by stimulating CD8 + IFNγ + lymphocytes and inducing cytotoxic effects. Thus, the function of CD151 in tumors is intricate and warrants further investigation. In this review, we discuss the diagnostic and prognostic potential of CD151, as well as its regulatory roles in solid cancers, including those of the digestive system, lung, breast, prostate, and gynecological tissues. Basic experiments and clinical data demonstrate the beneficial and detrimental effects of CD151 in malignancies and offer a path forward for future investigation.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"110"},"PeriodicalIF":5.3,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Costunolide inhibits the progression of TPA-induced cell transformation and DMBA/TPA-induced skin carcinogenesis by regulation of AKT-mediated signaling.","authors":"Kwanhwan Wi, Sun-Young Hwang, Young-Gwon Kim, Soong-In Lee, Cheol-Jung Lee, Geul Bang, Je-Ho Lee, Mee-Hyun Lee","doi":"10.1186/s12935-025-03742-w","DOIUrl":"10.1186/s12935-025-03742-w","url":null,"abstract":"<p><strong>Background: </strong>Costunolide (COS), a sesquiterpene lactone extracted from the roots of Saussurea costus, is known to possess anticancer properties in various cancers, including colon, oral, and lung cancers, but its mechanism of action in skin carcinogenesis has not yet been explored. Present study investigates the chemopreventive mechanism of COS on skin inflammation and carcinogenesis both in vitro and in vivo.</p><p><strong>Methods: </strong>The cytotoxicity of COS was examined on a normal murine epidermal cell line, JB6, by treating with COS using the WST-8 assay. Subsequently, the effect of COS on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cellular transformation was assessed through a soft-agar assay. Furtherly, cell cycle and apoptosis analysis and the expression of related proteins were determined via flow cytometry and Western blotting, respectively. The effects of COS on tumor promotion induced by DMBA/TPA treatment and the underlying molecular mechanisms in mouse skin carcinogenesis were identified through H&E staining and immunohistochemical analysis.</p><p><strong>Results: </strong>COS significantly inhibited colony growth and number in TPA-induced JB6 cells transformation, arrested the cell cycle at the G2/M phase, increased p21 expression, and decreased cyclin B expression. In addition, COS induced cell apoptosis and increased the related markers expression including cleaved caspase-3 and - 7. COS suppressed the expression of phosphorylated AKT and its downstream signaling proteins and effectively reduced the translocation of phosphorylated NF-κB from the cytosol to the nucleus. Moreover, COS reduced papilloma formation in mouse skin and inhibited hyperplasia and phosphorylated AKT expression in tissues.</p><p><strong>Conclusion: </strong>These results demonstrate that COS inhibits TPA-induced cellular transformation and skin carcinogenesis both in vitro and in vivo through the AKT signaling pathway. Our findings suggest the potential of COS as a chemopreventive agent for skin carcinogenesis, highlighting its significance for further investigation in cancer prevention and therapy.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"106"},"PeriodicalIF":5.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highly expressed GCN1 is associated with cancer progression and poor prognosis in hepatocellular carcinoma patients.","authors":"Zhongchao Zhang, Caijun Rao, Mingcun Hu, Wei Yan, Zhipeng Du","doi":"10.1186/s12935-025-03732-y","DOIUrl":"10.1186/s12935-025-03732-y","url":null,"abstract":"<p><strong>Background: </strong>General control non-derepressible protein 1 (GCN1), a ribosome-binding protein, has been implicated in the development and progression of multiple cancers. However, the potential role of GCN1 in hepatocellular carcinoma (HCC) has not yet been investigated.</p><p><strong>Methods: </strong>The expression of GCN1 in HCC was analyzed using multiple databases. Bioinformatics analysis was employed to investigate the correlation of GCN1 expression with clinical significance and immune infiltration in HCC. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, gene set enrichment analysis (GSEA), and in vitro experiments were conducted to study the function and potential mechanisms of GCN1 in HCC.</p><p><strong>Results: </strong>GCN1 was significantly upregulated in HCC, which was associated with worse clinicopathological features and poorer prognosis of the patients. GCN1 expression was closely associated with immune cell infiltration in HCC. GSEA analysis showed that GCN1 was involved in several tumor-related signaling pathways, including cell cycle, DNA replication, and Wnt signaling pathway. Knockdown of GCN1 inhibited the proliferation, invasion and migration of HCC cells, and also down-regulated the expression levels of cell cycle protein cyclin B1 (CCNB1), cyclin D1 (CCND1), and Wnt signaling pathway-related proteins Wnt3A and β-catenin.</p><p><strong>Conclusion: </strong>GCN1 overexpression was associated with HCC progression and poor prognosis, and GCN1 knockdown could suppress the proliferation, migration and invasion ability of HCC cells by regulating Wnt signaling pathway, suggesting the potential of GCN1 as a prognostic and therapeutic target for HCC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"107"},"PeriodicalIF":5.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatty acid metabolism related gene MECR contributes to the progression of prostate cancer.","authors":"Yifan Liu, Lilin Wan, Yuxuan Chen, Ruixin Zhang, Yi Xia, Ming Chen, Xiang Huang, Ruiji Liu","doi":"10.1186/s12935-025-03738-6","DOIUrl":"10.1186/s12935-025-03738-6","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer (PCa) is the most common urological malignancy and second only to lung cancer in incidence among men. Its prognosis varies widely due to its heterogeneity. Research indicates that fatty acid metabolism may play a role in tumor development.</p><p><strong>Methods: </strong>The gene expression profiles of PCa cell lines (GSE6919) in GEO database were analyzed to identify differentially expressed genes and their significance in relation to progression-free interval. The R package was employed to assess overall survival significance and clinicopathological features. The study investigated the effects of gene mutations and methylation on PCa and their correlation with immune cell infiltration in the tumor microenvironment, utilizing cBioPortal and UALCAN resources. TIMER was used in the TCGA project to compare the expression of MECR in tumours and in adjacent normal tissue for different tumours or for specific tumour subtypes. Furthermore, we examined the impact of hub genes on PCa progression through RT qPCR, immunohistochemistry, and cellular assays.</p><p><strong>Results: </strong>The MECR gene, which plays a role in fatty acid metabolism, has been implicated in the development and progression of PCa. Its expression levels are significantly associated with clinical features, survival outcomes, and prognosis in PCa. Comprehensive analyses of MECR mutations and methylation levels further underscore its involvement in the progression of prostate cancer. Additionally, MECR is closely associated with the immune microenvironment and immune cell infiltration in PCa. Furthermore, the in vitro and in vivo data indicated that MECR plays a role in PCa proliferation, migration, and invasion.</p><p><strong>Conclusion: </strong>MECR has significant potential for research and application in the assessment of PCa prognosis and the regulation of the immune microenvironment.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"105"},"PeriodicalIF":5.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing the therapeutic effectiveness of paclitaxel in chronic lymphocytic leukemia through the simultaneous inhibition of NOTCH1 and SF3B1.","authors":"Shiva Abolhasani, Armin Mahmoud Salehi Khesht, Atefeh Khodakarami, Ali Masjedi, Bentolhoda Rashidi, Sepideh Izadi, Fatemeh Karimian Noukabadi, Vahid Karpisheh, Khatereh Torabi Poudeh, Pooya Jalali, Zahra Salehi, Rafieh Bagherifar, Seyyed Sina Hejazian, AliAkbar Movassaghpour, Abbas Ali Hosseinpour Feizi, Farhad Jadidi","doi":"10.1186/s12935-025-03702-4","DOIUrl":"10.1186/s12935-025-03702-4","url":null,"abstract":"<p><strong>Background: </strong>Chemoresistance is still a significant obstacle to cancer therapy. Overexpression of the splicing factor 3b subunit 1 (SF3B1) and neurogenic locus notch homolog protein 1 (NOTCH1) factors is typically found in chronic lymphocytic leukemia (CLL), leading to the development of chemotherapy resistance.</p><p><strong>Objective: </strong>The current investigation aims to evaluate the chemosensitivity of CLL cells by blocking NOTCH1 and SF3B1 using chitosan lactate (CL) nanoparticles (NPs).</p><p><strong>Methods: </strong>We used CL-NPs loaded with anti-NOTCH1 and -SF3B1 small interfering RNAs (siRNAs) in combination with paclitaxel (PTX) to suppress NOTCH1 and SF3B1 in peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMCs) isolated from CLL cases to assess the impact of this therapeutic strategy on leukemic cell chemosensitivity. Further, the competing endogenous RNA (ceRNA) network that regulates NOTCH1 and -SF3B1 was constructed and enriched.</p><p><strong>Results: </strong>Our findings showed that CL-NPs loaded with anti-NOTCH1/-SF3B1 siRNAs-PTX significantly suppressed NOTCH1 and SF3B1 expression in PBMCs and BMMCs isolated from CLL cases in comparison with the untreated samples, leading to increased leukemic cell sensitivity to PTX and decreased the proliferative capacity of leukemic cells. The enrichment analysis highlighted the fundamental pathways where the NOTCH1- and SF3B1-associated ceRNA network exerts its influence in the context of CLL.</p><p><strong>Conclusions: </strong>This study implies the efficacy of combined therapy by CL-NPs loaded with anti-NOTCH1/-SF3B1 siRNAs and PTX as a novel therapeutic strategy for CLL, even though further studies are required to warrant the findings.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"104"},"PeriodicalIF":5.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intratumoral heterogeneity and drug resistance in cancer.","authors":"Yue-Chun Fu, Shao-Bo Liang, Min Luo, Xue-Ping Wang","doi":"10.1186/s12935-025-03734-w","DOIUrl":"10.1186/s12935-025-03734-w","url":null,"abstract":"<p><p>Intratumoral heterogeneity is the main cause of tumor treatment failure, varying across disease sites (spatial heterogeneity) and polyclonal properties of tumors that evolve over time (temporal heterogeneity). As our understanding of intratumoral heterogeneity, the formation of which is mainly related to the genomic instability, epigenetic modifications, plastic gene expression, and different microenvironments, plays a substantial role in drug-resistant as far as tumor metastasis and recurrence. Understanding the role of intratumoral heterogeneity, it becomes clear that a single therapeutic agent or regimen may only be effective for subsets of cells with certain features, but not for others. This necessitates a shift from our current, unchanging treatment approach to one that is tailored against the killing patterns of cancer cells in different clones. In this review, we discuss recent evidence concerning global perturbations of intratumoral heterogeneity, associations of specific intratumoral heterogeneity in lung cancer, the underlying mechanisms of intratumoral heterogeneity potentially leading to formation, and how it drives drug resistance. Our findings highlight the most up-to-date progress in intratumoral heterogeneity and its role in mediating tumor drug resistance, which could support the development of future treatment strategies.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"103"},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated analysis reveals an immune evasion prognostic signature for predicting the overall survival in patients with hepatocellular carcinoma.","authors":"Jiahua Wen, Kai Wen, Meng Tao, Zhenyu Zhou, Xing He, Weidong Wang, Zian Huang, Qiaohong Lin, Huoming Li, Haohan Liu, Yongcong Yan, Zhiyu Xiao","doi":"10.1186/s12935-025-03743-9","DOIUrl":"10.1186/s12935-025-03743-9","url":null,"abstract":"<p><strong>Background: </strong>The development of immunotherapy has enriched the treatment of hepatocellular carcinoma (HCC), but the efficacy is not as expected, which may be due to immune evasion. Immune evasion is related to the immune microenvironment of HCC, but there is little research on it.</p><p><strong>Methods: </strong>We employed unsupervised clustering analysis to categorize patients from TCGA based on 182 immune evasion-related genes (IEGs). We utilized single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT to calculate differences in immune cell infiltration between clusters. The differences in immune cells and immune-related pathways were assessed using GSEA. We constructed an immune escape prognosis signature (IEPS) using univariate Cox and LASSO Cox algorithms and evaluated the predictive performance of IEPS with receiver operating characteristic (ROC) curves and survival curves. Additionally, we established a nomogram for clinical application based on IEPS. IHC validated the expression of Carbamoyl phosphate synthetase 2, Aspartate transcarbamylase, and Dihydroorotase (CAD) and Phosphatidylinositol Glycan Anchor Biosynthesis Class U (PIGU) in HCC. We transfected liver cancer cell lines with siRNA and overexpression plasmids, and confirmed the relationship between CAD, PIGU, and the potential downstream TGF-β1 in HCC using qRT-PCR and Western blot. Finally, we validated the tumor response of CAD overexpression using an animal model.</p><p><strong>Results: </strong>Unsupervised clustering analysis based on IEGs divided HCC patients from TCGA into two groups. There were significant differences in prognosis and immune characteristics between the two groups of patients. Scoring of TCGA patients using IEPS revealed that higher scores were associated with poorer overall survival (OS). Validation was performed using the ICGC database. TIME analysis indicated that patients in the high-IEPS group were in an immunosuppressive state, possibly due to a significant increase in Treg infiltration. Compared to normal liver cells, HCC cells expressed higher levels of CAD and PIGU. Cellular experimental results showed a positive correlation between CAD, PIGU and the potential downstream TGF-β1 expression. Animal experiments demonstrated that CAD significantly promoted tumor progression, with an increase in Treg infiltration.</p><p><strong>Conclusion: </strong>IEPS has strong prognostic value for HCC patients, and CAD and PIGU provide perspectives on new biomarkers and therapeutic targets for HCC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"101"},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11916977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A combined gene signature model for predicting radiotherapy response and relapse-free survival in laryngeal squamous cell carcinoma.","authors":"Shiqi Gong, Liyun Yang, Meng Xu, Mingliang Xiang, Juntian Lang, Hao Zhang, Yamin Shan","doi":"10.1186/s12935-025-03739-5","DOIUrl":"10.1186/s12935-025-03739-5","url":null,"abstract":"<p><strong>Background: </strong>Radioresistance is a major challenge in radiotherapy for laryngeal squamous cell carcinoma (LSCC), and there is currently no effective method to predict radiosensitivity in LSCC patients. This study aimed to establish a prediction model for radiotherapy response based on gene expression.</p><p><strong>Methods: </strong>The datasets of LSCC were obtained from the ENT department of Shanghai Ruijin Hospital and The Cancer Genome Atlas (TCGA). Lasso regression and Cox regression were used to establish the prediction model based on gene expression. Weighted gene coexpression network analysis (WGCNA) was used to analyze the correlation between gene expression and clinical characteristics. RT-qPCR was used to detect gene expression in tumor tissue to verify the accuracy of the prediction model.</p><p><strong>Results: </strong>Using a cohort of LSCC cases receiving radiotherapy collected in the TCGA database, the 3 protein-coding genes (PCGs) signature model was identified for the first time as the predictor of relapse-free survival and radiosensitivity in LSCC patients. And we explored the potential clinical value of 3 PCGs and screened out 2 long non-coding RNAs (lncRNAs) potential associated with 3 PCGs. More importantly, the LSCC cases collected by our department were used to preliminarily verify the predictive power of the 3 PCGs signature model for the radiosensitivity of LSCC, and the significant correlation between the expression levels of the 3 PCGs and the 2 lncRNAs.</p><p><strong>Conclusion: </strong>We successfully establish a radiosensitivity prediction model based on the 3 PCGs Riskscore, which provides a theoretical basis for the decision-making of LSCC treatment options. Meantime, we preliminarily screen the potential associated lncRNAs of the 3 PCGs for further basic and clinical research.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"102"},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11916850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Broussoflavonol B induces S-phase arrest and apoptosis in pancreatic cancer cells by modulating the cell cycle checkpoint through inhibition of the AURKA/PLK1 pathway.","authors":"HyokChol Choe, Zhen Wang, Jianhua Huang, Yutong Yang, Zhihao Zhao, HyonSu Jo, HyonU Pak, Tanveer Ali, Kaiyue Ding, Junnan Ma, Lingzhi Li, Dong Shang, Lin Zhang","doi":"10.1186/s12935-025-03717-x","DOIUrl":"10.1186/s12935-025-03717-x","url":null,"abstract":"<p><strong>Background: </strong>Broussoflavonol B (Bf-B), a flavonoid compound identified in the roots of Daphne giraldii Nitsche, has been extensively investigated for its potential anti-inflammatory, antioxidant, and anticancer properties. However, the precise mechanism underlying the regulation of AURKA/PLK1 pathway-mediated cell cycle arrest by Bf-B in pancreatic cancer remains poorly understood.</p><p><strong>Purpose: </strong>The objective of this study was to investigate the inhibitory effect of Bf-B on pancreatic ductal adenocarcinoma (PDAC) and its underlying mechanism.</p><p><strong>Methods: </strong>A CCK8 assay was conducted to identify the flavonoids with the highest inhibitory activity against PANC-1, the pancreatic cancer cell line among the 25 flavonoids. Through bioinformatics analysis and molecular docking, the pathogenic targets of pancreatic cancer and flavonoid-related targets were explored, and the key targets and signaling pathways of drug intervention in pancreatic cancer were analyzed. The viability and migration ability of pancreatic cancer cells were assessed following treatment with Bf-B via the CCK8, colony formation, and wound healing assays. The cell cycle distribution and cell apoptosis were analyzed through flow cytometry and Hoechst staining. Western blotting and qPCR were employed to investigate the expression of relevant proteins and genes. For in vivo experiments, we employed a xenograft mouse model to evaluate the anticancer efficacy of Bf-B. Immunohistochemistry and immunofluorescence assays were employed to investigate the expression of relevant proteins.</p><p><strong>Results: </strong>In this study, the structure‒activity relationships of 25 flavonoids were evaluated. The results demonstrated that Bf-B with diisopentenyl has potent cytotoxic effects on PANC-1 cancer cells. AURKA, PLK1, and MET might serve as key targets for Bf-B inhibition of disease progression in PDAC patients. The results demonstrated that Bf-B inhibits the proliferation and migration of PANC-1 and BXPC-3 cells and induces cell cycle S-phase arrest, apoptosis, and DNA damage. Moreover, the results of western blot and qPCR experiments indicated that Bf-B exerts anticancer effects by downregulating the expression of the genes encoding AURKA/PLK1, the cell cycle checkpoint kinase ATR/CHK1/CDC25C, and Cyclin B1/CDK1 signaling pathway-related proteins and upregulating the expression of PP53, P21, and histone H2A. XS139ph expression. In xenograft-bearing mice, AURKA/PLK1 expression was reduced in a dose-dependent manner, accompanied by an increase in histone H2A. XS139ph expression.</p><p><strong>Conclusion: </strong>Bf-B might be a potent therapeutic agent for pancreatic cancer because of its ability to suppress the expression of AURKA/PLK1.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"100"},"PeriodicalIF":5.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11916852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZEB1 promotes the immune escape of ovarian cancer through the MCSF-CCL18 axis.","authors":"Yan-Ping Jin, Guo-Wei Li, Qian-Qian Xu, Xiao-Lan Wang","doi":"10.1186/s12935-025-03724-y","DOIUrl":"10.1186/s12935-025-03724-y","url":null,"abstract":"<p><p>This study aimed to determine the molecular mechanisms underlying immune escape in ovarian cancer. Samples of ovarian cancer were used to explore the regulatory pathways involved in the malignant phenotype. Tumor cell models with different levels of factor expression were constructed via transfection, and their regulation was determined through investigation of protein expressions. Moreover, our study aimed to investigate the effects of M2 polarization and TAMs aggregation on the apoptosis of CD8 + T-cells, and determine their regulatory axis. Results revealed ZEB1 may promote CCL18 expression via upregulation of MCSF concentration. Notably, high CCL18 expression levels were associated with the aggregation of M2-TAMs and the apoptosis of CD8 + T-cells. In addition, results of the present study demonstrated that the proliferation and invasion of ovarian cancer cells with high expression levels of proteins associated with ZEB1 signal pathway were increased. At the same time the growth rate of tumors in mice was reduced following ZEB1 knockdown, and the volume/weight of tumors were markedly decreased both in vitro and in vivo. Moreover, our results revealed that the aggregation of M2-TAMs and the apoptosis of CD8 + T-cells were significantly decreased in tumor cells following ZEB1 knockdown. Thus, these results verified that ZEB1 may promote the M2 polarization of TAMs via the MCSF axis, leading to the increased secretion of CCL18. Moreover, the MCSF axis may mediate immune escape through the induction of CD8 + T-cell apoptosis, ultimately promoting the malignant phenotype in ovarian cancer cells.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"95"},"PeriodicalIF":5.3,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}