Current cancer drug targets最新文献

{"title":"Long Non-Coding RNA HCP5 Affects Ferroptosis in Lung Adenocarcinoma through miR-17-5p/HOXA7 Axis.","authors":"Qingyun Pan, Zige Tang, Jiayu Zheng, Lingxin Yan, Quanfang Chen","doi":"10.2174/0115680096321714240909182553","DOIUrl":"https://doi.org/10.2174/0115680096321714240909182553","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis, a regulated cell death initiated by Fe-dependent lipoperoxidation, is closely linked to the development of lung adenocarcinoma (LUAD). LncRNA human leukocyte antigen complex P5 (HCP5) has been confirmed as oncogenic in LUAD, but its function in ferroptosis is unknown.</p><p><strong>Objective: </strong>Based on the previous bioinformatics mining of the ceRNA (competitive endogenous RNA) network HCP5/miR-17-5p/ Homeobox A7 (HOXA7) related to ferroptosis in LUAD, in this study, we characterized the cell-based experiments to validate the binding between the HCP5/miR-17-5p/HOXA7 axis and ferroptosis.</p><p><strong>Methods: </strong>The HCP5/miR-17-5p/HOXA7 linkage was identified by a two-luciferase reporter. Cell Counting Kit-8 (CCK-8) and Transwell assay were employed for the detection of viability, invasion, and migration of A549 cells, respectively. ACSL4 and SLC7A11 were associated with ferroptosis, MMP 9, vimentin, and E-cadherin, which were associated with migration and invasion and were assessed by WB and qRT-PCR. Fe2+ and malondialdehyde (MDA) were analyzed using kits.</p><p><strong>Results: </strong>Over-expression of HCP5 enhances the growth, invasion, and migration of A549 cells by adjusting miR-17-5P to increase the expression of HOXA7. In addition, the knock-down of HCP5 elevated miR-17-5p, which inhibited HOXA7 expression and suppressed ferroptosis and EMT in A549 cells.</p><p><strong>Conclusion: </strong>HCP5/miR-17-5p/HOXA7 can affect ferroptosis as well as the biological behavior of A549 cells.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FHOD3 Promotes the Progression of Lung Cancer by Regulating the Caspase-3-Mediated Signaling Pathway.","authors":"Zhonglu Peng, Junjie Wang, Zhenghang Huan, Chengmin Zhou, Zhifeng Li, Huilong Fang, Zhiying Yang, Dongyang He, Weiquan Xie","doi":"10.2174/0115680096330059240909172011","DOIUrl":"https://doi.org/10.2174/0115680096330059240909172011","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Lung cancer causes hundreds of thousands of deaths each year worldwide. FHOD3 was reported to accelerate the progression of brain cancer. However, its role in lung cancer is not clear. This study aimed to investigate the role of FHOD3 in lung cancer.</p><p><strong>Methods: </strong>The clinical significance of FHOD3 in lung cancer was analyzed based on the data from the TCGA database. The expression level of FHOD3 was detected by qPCR technology. Cell proliferation was detected by CCK-8 assay, and cell invasion was detected by transwell assay. The activity of caspase-3 was determined by the ELISA method, cell apoptosis was iden-tified by TUNEL assay, and protein expression was measured by western blotting technology.</p><p><strong>Results: </strong>Based on the TCGA data, FHOD3 was overexpressed in tumor tissues compared to the normal tissues. Patients with higher FHOD3 expression exhibited a worse survival rate. The expression levels of FHOD3 in lung cancer cell lines were much higher than that in normal cells. When FHOD3 was knocked down, the ability of cell proliferation and invasion was sig-nificantly inhibited. Cell apoptosis rate was increased reversely. The activity of caspase-3 was increased significantly. In addition, the expression level of cleaved caspase-3 was increased. The expression levels of Bax, caspase-8, and ICAD were also increased significantly. However, the expression of antiapoptotic molecule Bcl-2 was decreased reversely. This suggests that the caspase-3-mediated apoptosis signaling pathway was activated by FHOD3 knockdown.</p><p><strong>Conclusion: </strong>FHOD3 was overexpressed and negatively associated with survival rate in lung cancer patients. FHOD3 regulates cell proliferation, invasion, and apoptosis through the caspase-3-mediated signaling pathway. This study indicates that FHOD3 is an important gene contributing to the progression of lung cancer and might be a new drug target for the therapy of lung cancer.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal circRNAs: The Key Role and Potential Therapeutic Target in Gastric Cancer.","authors":"Yong Jin, Jingjing Wang, Chunwei Zhang, Jingjing Li, Chengyan Wei, Yuanzhi Zhou","doi":"10.2174/0115680096318527240909082011","DOIUrl":"https://doi.org/10.2174/0115680096318527240909082011","url":null,"abstract":"<p><p>A ring-stabilized endogenous non-coding RNA is called circular RNA (circRNA). Intercellular communication is mediated by exosomes, and circRNA is enriched and stabilized in exosomes. It has recently been demonstrated that cancer cells and tissues exhibit abnormal expression of exosomal circRNAs. By controlling angiogenesis, metabolism, metastasis, epithe-lial mesenchymal transition (EMT), tumor chemoresistance, immune evasion, and cell prolifera-tion, it may also have an impact on the development of different malignancies. Furthermore, ex-osomal circRNAs have strong tissue selectivity, stability, and other qualities that make them useful for diagnostic purposes. Consequently, exosomal circRNAs offer a wide range of poten-tial applications in the therapy of cancer and can be utilized as biomarkers and anti-tumor tar-gets. The features and purposes of circRNAs and exosomes are briefly discussed in this review, which also methodically explains the function and possible mechanism of the function of exo-somal circRNA in the onset of gastric cancer (GC). Furthermore, their clinical uses as targets and biomarkers for gastric cancers are also summarized and discussed in this work.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zinc Finger Protein 536 is a Potential Prognostic Biomarker that Promotes Neuroblastoma Progression via VEGFR2-PI3K-AKT Pathway.","authors":"Yuan Fang, Rui Dong, Shujing Wang, Lian Chen, Yizhen Wang, Qiang Wu","doi":"10.2174/0115680096332753240913104409","DOIUrl":"https://doi.org/10.2174/0115680096332753240913104409","url":null,"abstract":"<p><strong>Background: </strong>Neuroblastoma (NB) is a well-known pediatric malignancy intertwined with neurodevelopment. Previously implicated in neuronal differentiation, Zinc Finger Protein 536 (ZNF536) has emerged as a promising prognostic and immune-related biomarker in our pan-cancer analysis.</p><p><strong>Methods: </strong>Single-cell RNA transcriptome sequencing, bulk transcriptome analysis, and immuno-histochemistry were used to assess ZNF536 expression and its association with prognosis. Cell proliferation, migration, invasion, and differentiation in ZNF536-knockdown NB cell lines were detected to evaluate the effect of ZNF536 on tumor cells. Vascular Endothelial Growth Factor Receptor 2 (VEGFR2), a potential target of ZNF536, and its downstream PI3K/AKT signaling cascade were investigated using transcriptome sequencing, CUT&Tag, quantitative real-time PCR (qRT-PCR), and Western blotting. The role of ZNF536 in tumorigenesis and the potential regulation axis was evaluated in vivo using a BALB/c nude mouse xenograft tumor model.</p><p><strong>Results: </strong>ZNF536 mRNA and protein expression were significantly higher in NB patients with poor prognosis. In vitro, ZNF536 knockdown curtailed proliferation, migration, and invasion of NB cells while fostering differentiation. ZNF536 regulated VEGFR2 expression, thus activating the PI3K-AKT pathway. In vivo, ZNF536 knockdown reduced tumor growth and proliferation via the VEGFR2-PI3K-AKT pathway.</p><p><strong>Conclusion: </strong>ZNF536 resulted as a novel prognostic biomarker in NB, promoting oncogenesis through VEGFR2-PI3K-AKT signaling axis modulation, suggesting its therapeutic potential in managing NB progression.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of PANoptosis Subtypes to Assess the Prognosis and Immune Microenvironment of Lung Adenocarcinoma Patients: A Bioinformatics Combined Machine Learning Study.","authors":"Xiaofeng Zhou, Bolin Wang, Di Wu, Lu Gao, Zhihua Wan, Ruifeng Wu","doi":"10.2174/0115680096322045240902103219","DOIUrl":"https://doi.org/10.2174/0115680096322045240902103219","url":null,"abstract":"<p><strong>Background: </strong>PANoptosis, a novelty mechanism of cell death involving crosstalk between apoptosis, pyroptosis, and necroptosis, is strongly associated with tumor cell death and immunotherapy efficacy. However, its relevance in lung adenocarcinoma (LUAD) remains to be elucidated.</p><p><strong>Methods: </strong>In this study, we acquired 18 PANoptosis-related differentially expressed gene (PRDEG) of LUAD. Based on these genes, LUAD samples were identified with different sub-types by unsupervised clustering. Next, we compared the differences between the subtypes, including clinical features, immune microenvironment, and potentially sensitive drugs. Further-more, we used machine learning to identify hub prognostic PRDEGs, construct a risk score, and validate it on other external datasets. We incorporated the patient's clinical information and risk score into the proportional hazards model and lasso-cox models to find key prognostic features and constructed five prognostic models. The best model was identified via the area under the curve and validated on an external dataset.</p><p><strong>Results: </strong>LUAD patients were divided into two clusters named C1 and C2, respectively. The C2 cluster exhibited shorter survival time, more advanced tumor stage, higher suppressive immune cell scores, such as dendritic cells, and higher expression of inhibitory immune checkpoints, such as LAG3 and CD86. TIMP1, CAV1, and CD69 were recognized as key prognostic factors, and risk scores predicted survival with significant differences in the external validation set. Risk score and N-stage were identified as critical prognostic features. The Coxph model outper-formed other machine learning clinical models. The 1-, 3-, and 5-year time-ROCs in the exter-nal validation set were 0.55, 0.59, and 0.60, respectively.</p><p><strong>Conclusion: </strong>We demonstrated the potential of PANoptosis-based molecular clustering and prognostic features in predicting the survival of patients with LUAD as well as the tumor mi-croenvironment.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Clinicopathological and Prognostic Significance of the Expression of PD-L1 and MET Genes in Breast Cancer: Potential Therapeutic Targets.","authors":"Muhsen Al-Diabat, Nehad M Ayoub, Laith Al-Eitan, Moath Alshorman, Aymen Shatnawi","doi":"10.2174/0115680096333231240902070108","DOIUrl":"https://doi.org/10.2174/0115680096333231240902070108","url":null,"abstract":"<p><strong>Introduction: </strong>The heterogeneity of breast cancer requires exploring novel prognostic biomarkers as well as therapeutic targets for the treatment of the disease.</p><p><strong>Methods: </strong>The METABRIC dataset was used to describe the gene expression of the programmed death-ligand 1 (PD-L1) and the hepatocyte growth factor receptor (MET) and their association with the tumor clinicopathologic characteristics and overall survival in breast cancer.</p><p><strong>Results: </strong>The expression of the PD-L1 and MET genes correlated positively with the Nottingham Prognostic Index (NPI) (p=0.003 and p < 0.001, respectively). The expression of the two genes correlated inversely with luminal A and luminal B tumors (r= - 0.089, p= 0.021 and r= - 0.116, p= 0.013, respectively). The PD-L1 mRNA levels were significantly higher in hormone receptor-negative and HER2-positive tumors. MET mRNA expression levels were significantly higher in hormone receptor-negative, HER2-enriched, and non-luminal breast cancers. The PD-L1/MET double-high expression was associated with younger age of patients at diagnosis, higher NPI scores, larger tumors, advanced stage, high-grade, hormone receptor-negativity, HER2-positivity, and non-luminal tumors. None of the genes or their double expression status was significantly associated with overall survival in this analysis.</p><p><strong>Conclusion: </strong>The expression of the PD-L1 and MET genes is remarkably associated with worse tumor clinicopathologic features and poor prognosis in patients with breast cancer. Further investigations using combination drug regimens targeting PD-L1 and MET are important, particularly in breast tumors expressing high levels of both proteins.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Combination Therapy of Cyclophosphamide and Immunomodulating Agents in Cancer.","authors":"Siti Nursyahirah Bakar, Chin Siang Kue","doi":"10.2174/0115680096314791240830111909","DOIUrl":"https://doi.org/10.2174/0115680096314791240830111909","url":null,"abstract":"<p><p>Cyclophosphamide is a precursor of alkylating nitrogen mustard and was initially claimed to have antineoplastic and immunosuppressive properties. However, the role of cyclo-phosphamide as an immune activator has also been reported, depending on the dosage used. The application of lower-dose cyclophosphamide has emerged as a potential approach to cancer treatment. Cyclophosphamide selectively depletes regulatory T cells (Tregs), which dampens the immunological response, thereby rebalancing the immune system to allow other immune cells to act more efficiently. Cyclophosphamide can be either a friend or a foe in cancer treatment, de-pending on the therapeutic regime. The following questions remain to be answered: Can the cy-clophosphamide be used in the presence of other agents? Is there any single immunotherapeutic agent that acts synergistically with cyclophosphamide to effectively alter the immunosuppres-sive tumor microenvironment? This review emphasizes the role of cyclophosphamide as an im-mune modulator, both alone and in combination with other immunotherapeutic agents, for effec-tive cancer treatment in preclinical and clinical settings.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Immunotherapy in the Management of Advanced Hepatocellular Carcinoma: A Systematic Review.","authors":"Raja Narendra Divakar Addanki, Anjali Srikanth Mannava, Mustansir Abbas Ali, Hemasri Velmurugan, Pugazhenthan Thangaraju, Talagampala Sri Varshini","doi":"10.2174/0115680096309235240827052642","DOIUrl":"https://doi.org/10.2174/0115680096309235240827052642","url":null,"abstract":"<p><strong>Introduction: </strong>The most prevalent histologic subtype of primary liver cancer, hepato-cellular carcinoma, is also the third most lethal malignancy worldwide and a significant cause of cancer death. When diagnosed, it is frequently too late for curative therapies. To add to the difficulty, it is resistant to conventional systemic therapies like chemotherapy.</p><p><strong>Method: </strong>Re-cently, more attention has been given to the use of immunotherapy for this condition. Immuno-therapy has had a major impact on the outcome of several malignancies; several studies have revealed the potential role of immunotherapy in advanced hepatocellular carcinoma. To provide an overview of the current literature, justification, and clinical evidence for the use of immuno-therapy in advanced hepatocellular carcinoma, we employed a systematic literature review (SLR) approach in this work. Additionally, we explored the benefits and rationales of various treatment combinations and described the molecular mechanisms behind resistance to a number of immunotherapy drugs.</p><p><strong>Results: </strong>A total of 188 articles from credible journals published be-tween 2013 and August 7, 2023, were screened. Eight of those articles were chosen for in-depth study. This systematic review concluded that the current immunotherapeutic approaches have the potential to improve outcomes for aHCC patients; however, several clinical and biological hurdles have to be overcome, and predictive markers are still eagerly needed.</p><p><strong>Conclusion: </strong>To fully realize the potential of immunotherapy agents and their combination therapies to enhance health outcomes for patients with aHCC, additional investigation and research are required.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression, Characteristics, and Clinical Target Prediction of PIK3C3/ vps34 in Gastric Cancer.","authors":"Chenglou Zhu, Wenhan Liu, Mingxu Da","doi":"10.2174/0115680096334160240916102105","DOIUrl":"https://doi.org/10.2174/0115680096334160240916102105","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the expression pattern of phosphatidylinositol 3-kinase class III (PIK3C3/vps34) in gastric cancer (GC) tissues and their juxtaposed normal counterparts and its correlation with the clinicopathological attributes and prognostic outlook of afflicted individuals.</p><p><strong>Methods: </strong>Immunohistochemical (IHC) staining was used to ascertain the expression levels of PIK3C3/vps34 across 60 GC tissues juxtaposed with their normal counterparts. Statistical methodologies were used to scrutinize the correlation between PIK3C3/vps34 expression and clinicopathological features, along with prognostic implications for GC patients.</p><p><strong>Results: </strong>In GC tissues, the positive expression rate of PIK3C3/vps34 was 23.3% (14/60), which contrasted sharply with the markedly elevated rate of 66.7% (40/60) observed in adjacent tissues. The positive expression proportion of PIK3C3/vps34 within GC tissues exhibited a notable decrease than in adjacent tissues (P<0.05). The expression of PIK3C3/vps34 inverse-ly correlated with tumor size, degree of tissue differentiation, depth of tumor infiltration, and incidence of lymph node metastasis (P<0.05), whereas no significant associations were found with patient sex, age, tumor location, TNM staging, or distant metastasis (P > 0.05). As the tumor diameter increases, the degree of tissue differentiation diminishes, tumor infiltration depth intensifies, lymph node metastasis emerges, the TNM stage progresses, and PIK3C3/vps34 expression level within GC tissues declines correspondingly. Kaplan-Meier survival analysis unveiled a prolonged survival duration among GC patients exhibiting heightened PIK3C3/vps34 expression than in their counterparts with diminished expression (HR=0.66, 95% CI: 0.55-0.80), demonstrating statistical significance (P<0.05). Protein interaction analysis revealed noteworthy interactions involving PIK3C3 with Beclin 1, UVRAG, and ATG14.</p><p><strong>Conclusion: </strong>PIK3C3/vps34 is downregulated in GC tissues, exerting a pivotal role in tumorigenesis, and is intimately linked with the prognostic trajectory of GC patients. It may serve as a significant biomarker for prognostic evaluation and a promising molecular therapeutic target for GC.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-Activated Neutrophils Promote Lung Cancer Progression through the IL-8/PD-L1 Pathway.","authors":"Yiping Zheng, Jianfeng Cai, Qiuhong Ji, Luanmei Liu, Kaijun Liao, Lie Dong, Jie Gao, Yinghui Huang","doi":"10.2174/0115680096337237240909101904","DOIUrl":"https://doi.org/10.2174/0115680096337237240909101904","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer remains a major global health threat due to its complex microenvironment, particularly the role of neutrophils, which are crucial for tumor development and immune evasion mechanisms. This study aimed to delve into the impact of lung cancer cell-conditioned media on neutrophil functions and their potential implications for lung cancer progression.</p><p><strong>Methods: </strong>Employing in vitro experimental models, this study has analyzed the effects of lung cancer cell-conditioned media on neutrophil IL-8 and IFN-γ secretion, apoptosis, PD-L1 expression, and T-cell proliferation by using techniques, such as ELISA, flow cytometry, immunofluorescence, and CFSE proliferation assay. The roles of IL-8/PD-L1 in regulating neutrophil functions were further explored using inhibitors for IL-8 and PD-L1.</p><p><strong>Results: </strong>Lung cancer cell lines were found to secrete higher levels of IL-8 compared to normal lung epithelial cells. The conditioned media from lung cancer cells significantly reduced apoptosis in neutrophils, increased PD-L1 expression, and suppressed T-cell proliferation and IFN-γ secretion. These effects were partially reversed in the presence of IL-8 inhibitors in Tumor Tissue Culture Supernatants (TTCS), while being further enhanced by IL-8. Both apoptosis and PD-L1 expression in neutrophils demonstrated dose-dependency to TTCS. Additionally, CFSE proliferation assay results further confirmed the inhibitory effect of lung cancer cell-conditioned media on T-cell proliferation.</p><p><strong>Conclusion: </strong>This study has revealed lung cancer cell-conditioned media to modulate neutrophil functions through regulating factors, such as IL-8, thereby affecting immune regulation and tumor progression in the lung cancer microenvironment.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}