Cancer Cell International最新文献

{"title":"EGFR-to-Src family tyrosine kinase switching in proliferating-DTP TNBC cells creates a hyperphosphorylation-dependent vulnerability to EGFR TKI.","authors":"Nazia Chaudhary, Bhagya Shree Choudhary, Anusha Shivashankar, Subhakankha Manna, Khyati Ved, Shagufa Shaikh, Sonal Khanna, Jeetnet Baar, Jagruti Dani, Sarthak Sahoo, R Soundharya, Mohit Kumar Jolly, Nandini Verma","doi":"10.1186/s12935-025-03691-4","DOIUrl":"10.1186/s12935-025-03691-4","url":null,"abstract":"<p><p>Triple-Negative Breast Cancer (TNBC) is the most aggressive type of breast malignancy, with chemotherapy as the only mainstay treatment. TNBC patients have the worst prognoses as a large fraction of them do not achieve complete pathological response post-treatment and develop drug-resistant residual disease. Molecular mechanisms that trigger proliferation in drug-resistant chemo-residual TNBC cells are poorly understood due to the lack of investigations using clinically relevant cellular models. In this study, we have established TNBC subtype-specific cellular models of proliferating drug-tolerant persister (PDTP) cells using different classes of chemotherapeutic agents that recapitulate clinical residual disease with molecular heterogeneity. Analysis of total phospho-tyrosine signals in TNBC PDTPs showed an enhanced phospho-tyrosine content compared to the parental cells (PC). Interestingly, using mass-spectrometry analysis, we identified a dramatic decrease in epidermal growth factor receptor (EGFR) expression in the PDTPs, while the presence of hyper-activated tyrosine phosphorylation of EGFR compared to PC. Further, we show that EGFR has enhanced lysosomal trafficking in PDTPs with a concomitant increase in N-Myc Downstream Regulated-1 (NDRG1) expression that co-localizes with EGFR to mediate receptor degradation. More surprisingly, we found that reduced protein levels of EGFR are coupled with a robust increase in Src family kinases, including Lyn and Fyn kinases, that creates a hyper-phosphorylation state of EGFR-Src tyrosine kinases axis in PDTPs and mediates downstream over-activation of STAT3, AKT and MAP kinases. Moreover, paclitaxel-derived PDTPs show increased sensitivity to EGFR TKI Gefitinib and its combination with paclitaxel selectively induced cell death in Paclitaxel-derived PDTP (PDTP-P) TNBC cells and 3D spheroids by strongly downregulating phosphorylation of EGFR-Src with concomitant downregulation of Lyn and Fyn tyrosine kinases. Collectively, this study identifies a unique hyper-phosphorylation cellular state of TNBC PDTPs established by switching of EGFR-Src family tyrosine kinases, creating a vulnerability to EGFR TKI.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"55"},"PeriodicalIF":5.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456992","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":"Correction: Epidermal growth factor receptor ligands enriched in follicular fluid exosomes promote oncogenesis of fallopian tube epithelial cells.","authors":"Aye Aye Khine, Pao-Chu Chen, Ying-Hsi Chen, Sung-Chao Chu, Hsuan-Shun Huang, Tang-Yuan Chu","doi":"10.1186/s12935-025-03684-3","DOIUrl":"10.1186/s12935-025-03684-3","url":null,"abstract":"","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"54"},"PeriodicalIF":5.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456990","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":"CircRNA hsa_circ_0004781 promoted cell proliferation by acting as a sponge for miR-9-5p and miR-338-3p and upregulating KLF5 and ADAM17 expression in pancreatic ductal adenocarcinoma.","authors":"Kun-Lin Lee, Jun-Jen Liu, Wei-Jan Huang, Ching-Sheng Hung, Yu-Chih Liang","doi":"10.1186/s12935-025-03687-0","DOIUrl":"10.1186/s12935-025-03687-0","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of solid tumor, and novel strategies must be developed for treating it. Previous studies predominantly utilized circular RNA (circRNA) expression plasmids incorporating Alu elements to facilitate the indirect expression of circRNA.</p><p><strong>Methods: </strong>Public databases and bioinformatics tools were used to identify hsa_circ_0004781 that is highly expressed in PDAC and its potential microRNA (miRNA) targets and corresponding mRNA targets. Real hsa_circ_0004781, which is identical to the native form of hsa_circ_0004781 without any exogenous sequences, was prepared through in vitro transcription by using a ribozyme and ion-pair reversed-phase high-performance liquid chromatography (IP-RP HPLC). The biological functions of hsa_circ_0004781 were evaluated using loss-of-function and gain-of-function approaches with circRNA expression plasmids and real hsa_circ_0004781.</p><p><strong>Results: </strong>Knockdown of hsa_circ_0004781 inhibited the proliferation and migration of PDAC cells, whereas its overexpression produced opposite effects. Hsa_circ_0004781 was identified as a sponge for miR-9-5p and miR-338-3p, and its expression was negatively correlated with that of these miRNAs. Among the targets of miR-9-5p and miR-338-3p, Kruppel-like factor 5 (KLF5) and a disintegrin and metalloproteinase domain 17 (ADAM17) were negatively correlated with survival in patients with PDAC and were inversely regulated by these miRNAs. Furthermore, real hsa_circ_0004781 exhibited the same effects as those of the circRNA expression plasmids.</p><p><strong>Conclusions: </strong>This study is the first to use real circRNAs to validate results obtained using circRNA expression plasmids. The results suggest that hsa_circ_0004781 functions as an oncogene, promoting the proliferation of PDAC cells through the miR-9-5p/KLF5 and miR-338-3p/ADAM17 axes. Therefore, hsa_circ_0004781 might be a therapeutic target for PDAC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"56"},"PeriodicalIF":5.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456985","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":"Esketamine reduces postoperative depression in breast cancer through TREK-1 channel inhibition and neurotransmitter modulation.","authors":"Jiachi Xu, Mingcan Li, Yu Hu, Qin Yang, Qiang Long, Hui Zhou","doi":"10.1186/s12935-025-03664-7","DOIUrl":"10.1186/s12935-025-03664-7","url":null,"abstract":"<p><p>Postoperative depression significantly affects the quality of life of breast cancer patients. This study explores the potential therapeutic effects of esketamine on postoperative depression through modulation of the TREK-1 two-pore domain potassium channel. We analyzed data from 54 female breast cancer patients who underwent surgery at our hospital between 2019 and 2023, dividing them into experimental and control groups based on esketamine treatment. Transcriptomic sequencing of hippocampal neurons from rats identified potassium ion-related pathways and key regulatory genes, including TREK-1, influenced by esketamine. In vitro studies showed that esketamine primarily alleviates depressive symptoms by inhibiting TREK-1 protein expression, enhancing GABA neurotransmitter release, and improving neuronal activity, while overexpression of TREK-1 reversed these effects. Esketamine's inhibition of TREK-1 channels and promotion of hippocampal neuron activity effectively alleviate postoperative depression in breast cancer patients, suggesting a novel therapeutic strategy.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"51"},"PeriodicalIF":5.3,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448213","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":"Recent advancements in nanomaterial-based biosensors for diagnosis of breast cancer: a comprehensive review.","authors":"Yalda Yazdani, Fereshtehsadat Jalali, Habib Tahmasbi, Mitra Akbari, Neda Talebi, Seyed Abbas Shahrtash, Ahmad Mobed, Mahsa Alem, Farhood Ghazi, Mehdi Dadashpour","doi":"10.1186/s12935-025-03663-8","DOIUrl":"10.1186/s12935-025-03663-8","url":null,"abstract":"<p><p>Researchers have found that mutations in the BRCA gene associated with breast cancer have a 40-50% chance of being associated with high risk for hereditary breast cancer (BC). Therefore, detecting BRCA1 is crucial for genetic analysis, early detection, and clinical treatment of BC. Traditional detection methods for BRCA1 include high-performance liquid chromatography (HPLC), single-strand conformation polymorphism assays (SSCP), PCR, real-time PCR, and DNA sequencing. However, these methods are limited by cost, analysis time, and complexity. Therefore, it is necessary to develop an ultrasensitive, fast, low-cost, simple method for BRCA1 detection. In recent years, various BC biosensing strategies have been investigated, including optical, electrical, electrochemical, and mechanical biosensing. In particular, the high sensitivity and short detection times of electrochemical biosensors make them suitable for recognizing BC biomarkers. Additionally, the sensitivity of electrochemical biosensors can be increased by incorporating nanomaterials. In this regard, the main focus of the present study is the introduction of common methods for diagnosing the BRCA-1/2 genes. In addition to introducing biosensors as an efficient tool, it also discusses the latest and most significant biosensors developed for detecting the BRCA gene.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"50"},"PeriodicalIF":5.3,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448222","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":"Potential value of immunogenic cell death related-genes in refining European leukemiaNet guidelines classification and predicting the immune infiltration landscape in acute myeloid leukemia.","authors":"Changqing Jiao, Xiaoyu Ma, Jianling Cui, Bobin Su, Fei Xu, Enbo Chen, Junjie Zhou, Jifei Dai, Mengya Pan, Zhangbiao Long, Jian Ge","doi":"10.1186/s12935-025-03670-9","DOIUrl":"10.1186/s12935-025-03670-9","url":null,"abstract":"<p><p>Immunogenic cell death (ICD) is the kind of cell death that triggers the immune system. It affects several tumors, whereas its significance for prognosis in acute myeloid leukemia (AML) remains uncertain. AML categorization by cytogenetic variables is inaccurate. In addition, risk stratification of AML based on cytogenetics is imprecise. The data of AML patients were extracted from 4 databases, a total of 1,537 patients. Univariate and LASSO Cox regression analyses were conducted to construct an ICD risk signature (ICDRS). The ICDRS showed strong prognostic value for AML through Kaplan-Meier, Cox, ROC analyses and nomogram. Combining the ICDRS with the European LeukemiaNet (ELN) classification to redefine the risk stratification can better predict the prognosis of AML. Moreover, the ICDRS was examined to identify gene functional enrichment, immunological characteristics, drug susceptibility, and somatic mutation, which revealed considerable variations among different risk categories. We further validated the expression of ICDRS in the AML bone marrow microenvironment by single-cell RNA (scRNA) analysis. Ultimately, the functional role of CASP1 was proven in AML by a series of in-vitro experiments. Our study highlights the significant impact of ICDRS on AML, which may improve ELN risk classification, predict immune landscapes, and guide personalized therapy.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"52"},"PeriodicalIF":5.3,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448219","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":"Comprehensive network pharmacology and experimental study to investigate the effect and mechanism of solasonine on breast carcinoma treatment.","authors":"Wenkai Ge, Min Gao, Yingqi Dai, Gang Zheng, Li Yang, Wenshu Zuo, Xingsong Tian","doi":"10.1186/s12935-025-03665-6","DOIUrl":"10.1186/s12935-025-03665-6","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis is a therapeutic strategy for breast carcinoma (BC). Solasonine (SS) was linked to ferroptosis as a tumor suppressor. However, whether SS could treat BC by activating ferroptosis and its underlying mechanisms has not been reported.</p><p><strong>Methods: </strong>We obtained the intersection of genes targeting SS and BC disease through network pharmacology. Bioinformatics analysis revealed that the intersection genes were primarily enriched in the extracellular signal-regulated kinase 2/mitogen-activated protein kinase (ERK2/MAPK) signaling pathway. The interaction modes of SS with ERK2 and epidermal growth factor receptor (EGFR) were simulated by molecular docking. We further detected the expressions of ERK2 and p-ERK2 in BC patients and the correlation between ERK2/p-ERK2 and ferroptosis. The effects and mechanism of SS on ferroptosis in BC were validated by mutation plasmids construction, immunohistology, wound healing, transwell assay, and western blotting using in vitro and in vivo models.</p><p><strong>Results: </strong>ERK2 and p-ERK2 were up-regulated in BC patients, and the ERK2/p-ERK2 ratio was negatively correlated with ferroptosis. Molecular docking indicated that SS could bind to ERK2 and EGFR to inhibit the activity of the ERK2/MAPK pathway. In vitro and in vivo experiments confirmed that SS induced ferroptosis by inhibiting the ERK2/MAPK pathway, inhibiting proliferation, migration, and invasion of BC cells.</p><p><strong>Conclusion: </strong>SS could inactivate the ERK2/MAPK pathway, thereby inducing ferroptosis and further inhibiting BC cell proliferation, migration, and invasion. This study clarified the potential mechanism of SS in BC and provided a theoretical basis for its clinical application.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"49"},"PeriodicalIF":5.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440231","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":"Mcl-1 downregulation enhances BCG treatment efficacy in bladder cancer by promoting macrophage polarization.","authors":"Caixia Tan, Chen Li, Ruihan Ge, Wei Zhang, Ziyi Wu, Shengpeng Wang, Haotian Cui, Xinmin Wang, Le Zhang","doi":"10.1186/s12935-025-03676-3","DOIUrl":"10.1186/s12935-025-03676-3","url":null,"abstract":"<p><strong>Background: </strong>Bacillus Calmette-Guérin (BCG) is the primary method of postoperative perfusion treatment for bladder cancer. The myeloid cell leukemia gene-1 (Mcl-1) is closely associated with the development of malignant tumors. Previous research by our group has demonstrated that downregulating Mcl-1 using shRNA can enhance the efficacy of BCG treatment in bladder cancer. This study aims to investigate the impact of Mcl-1 downregulation in combination with BCG treatment on bladder cancer, macrophage polarization, and the underlying mechanism of action, with the goal of reducing recurrence and metastasis in bladder cancer.</p><p><strong>Methods: </strong>The GSE190529 dataset was analyzed to identify differential genes for enrichment analysis. The WGCNA algorithm was then employed to pinpoint gene modules closely associated with the Mcl-1 gene. The overlapping genes between these modules and the differentially expressed genes were subjected to enrichment analysis in GO and KEGG pathways to unveil crucial signaling pathways. In vitro experiments involved the co-culture of Raw264.7 macrophages and MB49 to establish a tumor microenvironment model, while in vivo experiments utilized an MNU-induced rat bladder cancer model. Various methods including Enzyme-Linked Immunosorbent Assay (ELISA), Western blot, immunofluorescence, HE staining, etc. were utilized to assess macrophage polarization and the expression of proteins linked to the ASK1/MKK7/JNK/cJUN signaling pathway.</p><p><strong>Results: </strong>Bioinformatics analysis indicates that the therapeutic mechanism of Mcl-1 in BCG treatment for bladder cancer may be linked to the Mitogen-Activated Protein Kinase (MAPK) signaling pathway. Both in vivo and in vitro experiments have demonstrated that the combination of BCG treatment and Mcl-1shRNA intervention results in elevated expression of M1 markers (TNF-α, CD86, INOS) and reduced expression of M2 markers (IL-10, CD206, Arg-1). Moreover, there was a notable increase in protein levels of P-ASK1, P-MKK7, P-JNK, P-cJUN, and CX43, leading to a significant rise in the apoptosis rate of bladder cancer cells and diminished proliferation, migration, and invasion capabilities. The expression of these markers can be reversed by employing the JNK signaling pathway inhibitor SP600125.</p><p><strong>Conclusion: </strong>Down-regulation of Mcl-1 promotes the polarization of macrophages towards the M1 type through activation of the ASK1/MKK7/JNK signaling pathway. This enhances intercellular communication and improves the efficacy of BCG in bladder cancer treatment.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"48"},"PeriodicalIF":5.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11830210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425068","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":"The role of mitochondrial biogenesis, mitochondrial dynamics and mitophagy in gastrointestinal tumors.","authors":"Yihong Liu, Hao Wang, Shen Zhang, Na Peng, Shuangshuang Hai, Haibo Zhao, Jingwei Liu, Weixin Liu","doi":"10.1186/s12935-025-03685-2","DOIUrl":"10.1186/s12935-025-03685-2","url":null,"abstract":"<p><p>Gastrointestinal tumors remain the leading causes of cancer-related deaths, and their morbidity and mortality remain high, which imposes a great socio-economic burden globally. Mitochondrial homeostasis depend on proper function and interaction of mitochondrial biogenesis, mitochondrial dynamics (fission and fusion) and mitophagy. Recent studies have demonstrated close implication of mitochondrial homeostasis in gastrointestinal tumorigenesis and development. In this review, we summarized the research progress on gastrointestinal tumors and mitochondrial quality control, as well as the underlying molecular mechanisms. It is anticipated that the comprehensive understanding of mitochondrial homeostasis in gastrointestinal carcinogenesis would benefit the application of mitochondria-targeted therapies for gastrointestinal tumors in future.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"46"},"PeriodicalIF":5.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425093","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":"Mechanistic insights of lenvatinib: enhancing cisplatin sensitivity, inducing apoptosis, and suppressing metastasis in bladder cancer cells through EGFR/ERK/P38/NF-κB signaling inactivation.","authors":"Chih-Hung Chiang, Jr-Di Yang, Wei-Lin Liu, Fang-Yu Chang, Che-Jui Yang, Kai-Wen Hsu, I-Tsang Chiang, Fei-Ting Hsu","doi":"10.1186/s12935-024-03597-7","DOIUrl":"10.1186/s12935-024-03597-7","url":null,"abstract":"<p><strong>Background: </strong>The persistent activation of the epidermal growth factor receptor (EGFR) leads to the activation of downstream oncogenic kinases and transcription factors, resulting in tumor progression and an increased resistance to cisplatin in bladder cancer (BC) cells. Lenvatinib, an oral multikinase inhibitor, has the potential to offer therapeutic benefits as an adjuvant treatment for BC patients. The investigation into its application in bladder cancer treatment is a valuable endeavor. The primary goal of this study is to confirm the effectiveness and mechanism of lenvatinib in inhibiting the progression of BC and enhancing the anticancer efficacy of cisplatin.</p><p><strong>Materials: </strong>Three BC cell lines, namely, TSGH-8301, T24, and MB49, along with an MB49-bearing animal model, were utilized in this study.</p><p><strong>Results: </strong>In vitro experiments utilizing MTT assays demonstrated that lenvatinib sensitized BC cells to cisplatin, exhibiting a synergistic effect. Flow cytometry indicated apoptotic events and signaling, presenting that lenvatinib effectively induced apoptosis and triggered extrinsic/intrinsic apoptotic pathways. In vivo studies using a mouse model of BC confirmed the antitumor efficacy of lenvatinib, demonstrating significant tumor growth suppression without inducing toxicity in normal tissues. Western blotting analysis and immunohistochemistry stain revealed EGF-phosphorylated EGFR and EGFR-mediated ERK/P38/NF-κB signaling were suppressed by treatment with lenvatinib. In addition, lenvatinib also suppressed anti-apoptotic (MCL1, c-FLIP, and XIAP) and metastasis-related factors (Twist, Snail-1, ZEB-1, ZEB-2, and MMP9) and promoted epithelial markers (E-cadherin) while reducing mesenchymal markers (N-cadherin).</p><p><strong>Conclusion: </strong>In conclusion, the induction of apoptosis and the inhibition of EGFR/ERK/P38/NF-κB signaling are correlated with lenvatinib's ability to hinder tumor progression and enhance the cytotoxic effects of cisplatin in bladder cancer. These findings underscore the potential of lenvatinib as a therapeutic option for bladder cancer, either as a standalone treatment or in combination with cisplatin.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"47"},"PeriodicalIF":5.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425085","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}