PTEN诱导激酶1抵抗胃癌细胞凋亡并诱导奥沙利铂耐药  

PINK1 Inhibited theapoptosis of gastric cancer cells and induced chemo⁃resisitance to oxaliplatin

作　　者：吴珍珍[1] 刘志宏 杨楠彦 吴晶晶 梁俊广 孙丽[1] WU Zhenzhen;LIU Zhihong;YANG Nanyan;WU Jingjing;LIANG Junguang;SUN Li(Department of Oncology,the First Affiliated Southern Hospital of Southern Medical University,Guangzhou 510515,China)

机构地区：[1]南方医科大学南方医院肿瘤内科,广州510515

出　　处：《实用医学杂志》2020年第20期2769-2774,共6页The Journal of Practical Medicine

基　　金：国家自然科学基金面上项目(编号:81972292);广东省自然科学基金--博士启动项目(编号:2015A030310085);中国博士后科学基金第11批特别资助项目(编号:C1090147)。

摘　　要：目的探讨PTEN诱导激酶1(PTEN-induced kinas 1,PINK1)对于胃癌恶性生物学行为的作用。方法采用小干扰RNA(small interfering RNA,siRNA)干扰技术下调胃癌细胞中PINK1的表达,利用MTT法、划痕实验及Transwell实验检测下调PINK1表达后胃癌细胞的增殖、迁移能力改变;通过临床资料分析及MTT实验探索下调PINK1表达对于奥沙利铂敏感性的作用。结果下调PINK1表达可显著抑制胃癌细胞增殖、迁移及侵袭能力,促进活性氧(reactive oxygen species,ROS)的生成诱导凋亡,有效增加奥沙利铂的药物敏感性。结论PINK1可能是胃癌的潜在治疗靶点;下调PINK1表达可抑制胃癌的恶性生物学行为,增强奥沙利铂敏感性,与化疗有协同增敏的作用。Objective The aim of this research was to investigate the effects of PTEN⁃induced kinas 1(PINK1)on the malignant biological behavior of gastric cancer(GC).Methods PINK1 expression was downreg⁃ulated by small interfering RNA(siRNA)in GC cells.MTT assay,Wound healing assay and Transwell assay were conducted to explore the role of PINK1 in GC cells′proliferation and migration.Survival analysis and MTT experiments were applied subsequently to find out the effect of PINK1 on chemosensitivity of oxaliplatin.Results Down⁃regulation of PINK1 significantly inhibited the proliferation,migration and invasion of gastric cancer cells.Inhibition of PINK1 in GC cells could promote the production of reactive oxygen species(ROS)and induced apoptosis⁃related geen Bcl⁃2 upregulationand furtherly induce GC cells deaths.Finally,PINK1 downregulation effectively increased the drug sensitivity of GC cells to oxaliplatin,which highly suggested a chemoresistance role of PINK1 in GC.Conclusion PINK1 may be a potential therapeutic target for GC;down⁃regulation of PINK1 could inhibit the malignant biological behavior of GC cells,enhance the sensitivity of oxaliplatin,and synergistic sensitization with chemotherapy.

关 键 词：PINK1 胃癌 细胞凋亡 化疗敏感性 奥沙利铂 耐药 

分 类 号：R363[医药卫生—病理学]