实用医学杂志2025，Vol.41Issue(4)：490-499,10.DOI:10.3969/j.issn.1006-5725.2025.04.005
CCCTC结合因子通过抵抗凋亡促进奥沙利铂相关胃癌药物耐受细胞形成
CCCTC-binding factors promote the formation of oxaliplatin related gastric cancer drug-tolerant cells by resisting apoptosis
摘要
Abstract
Objective To investigate the role of CCCTC-binding factor(CTCF)in the development of oxaliplatin(OXA)-induced gastric cancer drug-tolerant cells(DTCs)and to preliminarily elucidate its underlying mechanisms.Methods The DTCs model of gastric cancer was established by treating MGC803 cells with OXA.Overexpression and knockdown of CTCF in MGC803 cells were performed to observe their effects on the formation of DTCs in gastric cancer.Additionally,Bcl2-like protein 1(BCL2L1)was knocked down in CTCF-overexpressing cells,and its impact on DTCs formation was evaluated.Flow cytometry was used to analyze the effects of varying CTCF/BCL2L1 expression levels on the apoptosis of gastric cancer cells under OXA treatment.Immunohistochemistry(IHC)was employed to detect the expression levels of CTCF/BCL2L1 in gastric cancer tissues,and the therapeutic outcomes of neoadjuvant chemotherapy in patients with different CTCF/BCL2L1 expression levels were assessed.Results Gastric cancer DTCs can be obtained following a regimen of continuous treatment of MGC803 cells with a specific concentration of oxaliplatin(OXA,1.5 μmol/L)for 5 days,followed by an additional 5-day culture period post-treatment cessation.The upregulation of CTCF has been shown to facilitate the formation of DTCs in gastric cancer,whereas its downregulation inhibits this process(P<0.05).In MGC803 gastric cancer cells,the expression level of BCL2L1 is positively correlated with that of CTCF.Knockdown of BCL2L1 in MGC803 cells overexpressing CTCF can reverse the pro-DTC formation effect of CTCF(P<0.05).Overexpression of CTCF confers resistance to OXA-induced apoptosis in gastric cancer cells,and this anti-apoptotic effect can be reversed by BCL2L1 knockdown in MGC803 cells overexpressing CTCF(P<0.05).In the tumor tissues of the majority of gastric cancer patients,the expression levels of BCL2L1 are positively correlated with those of CTCF,and the efficacy of neoadjuvant chemotherapy is notably reduced in patients with high expression of the CTCF/BCL2L1 axis compared to those with low expression(P<0.05).Conclusion CTCF promotes the formation of OXA-related gas-tric cancer DTCs by upregulating BCL2L1 expression and inhibiting apoptosis,making the CTCF/BCL2L1 axis a potential therapeutic target for DTCs in gastric cancer.关键词
胃癌/奥沙利铂/药物耐受细胞/凋亡/CCCTC结合因子/BCL2样蛋白1Key words
gastric cancer/oxaliplatin/drug tolerant cells/apoptosis/CTCF/BCL2L1分类
临床医学引用本文复制引用
李宗林,冯春林,刘欣,舒星铭,宋敏..CCCTC结合因子通过抵抗凋亡促进奥沙利铂相关胃癌药物耐受细胞形成[J].实用医学杂志,2025,41(4):490-499,10.基金项目
国家自然科学基金项目(编号:81803019) （编号:81803019）
四川省科技计划重点研发项目(编号:2023YFS0320) （编号:2023YFS0320）
泸州市科技局研究项目(编号:2022-JYJ-135) （编号:2022-JYJ-135）
