新型双胍衍生物1-正戊基-5-(4-三氟甲氧基苯基)双胍联合奥希替尼抑制膀胱癌细胞增殖  

A novel guanidine derivative 1-n-pentyl-5-(4-trifluoromethoxyphenyl)biguanide combined with osimertinib inhibited the proliferation of bladder cancer cells

作　　者：彭妍 周晓辰 谢乐静 章行健 肖迪 杨小平[1] PENG Yan;ZHOU Xiaochen;XIE Lejing;ZHANG Xingjian;XIAO Di;YANG Xiaoping(Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province,School of Medicine,Hunan Normal University,Changsha,410013,Hunan,China)

机构地区：[1]湖南师范大学医学院小分子靶向药物研究与创制湖南省重点实验室,湖南长沙410013

出　　处：《肿瘤药学》2024年第1期53-58,共6页Anti-Tumor Pharmacy

基　　金：国家级大学生创新创业训练计划支持项目(202210542030、S202310542006)。

摘　　要：目的探讨新型双胍衍生物1-正戊基-5-(4-三氟甲氧基苯基)双胍(5C)、奥希替尼单用及联用对膀胱癌的抑制作用及机制。方法采用MTT实验、细胞克隆实验检测5C、奥希替尼单用及联用对膀胱癌细胞增殖、集落形成的影响。采用Western blotting检测5C联合奥希替尼对表皮生长因子受体(EGFR)及其下游信号通路的影响。结果5C、奥希替尼单用均可显著抑制膀胱癌细胞增殖和集落形成,且二者联用能更好地抑制膀胱癌细胞的增殖与集落形成能力。机制研究表明,5C与奥希替尼联用能显著抑制EGFR及其下游信号通路Akt/Erk的磷酸化。结论5C联合奥希替尼可通过下调EGFR及其下游信号通路抑制膀胱癌细胞生长。Objective To investigate the inhibitory effect and mechanism of a novel guanidine derivative,1-n-pentyl-5-(4-trifluoromethoxyphenyl)biguanide(5C)and osimertinib alone or in combination on bladder cancer.Methods MTT assay and cell colony formation assay were used to detect the effects of 5C and osimertinib alone or in combination on the proliferation and colo-ny formation of bladder cancer cells.Western blotting was used to detect the effects of 5C combined with osimertinib on the epi-dermal growth factor receptor(EGFR)and its downstream signaling pathways.Results 5C or osimertinib alone significantly inhib-ited the proliferation and colony formation of bladder cancer cells,and the combination of 5C and osimertinib could better inhibit the proliferation and colony formation of bladder cancer cells.Mechanism studies showed that 5C combined with osimertinib could significantly inhibit the phosphorylation of EGFR and its downstream signaling pathway Akt/Erk.Conclusion 5C com-bined with osimertinib could inhibit the growth of bladder cancer cells by down-regulating EGFR and its downstream signaling pathway.

关 键 词：膀胱癌 奥希替尼 双胍类衍生物 联合用药 EGFR 

分 类 号：R737.14[医药卫生—肿瘤]