DPC4基因通过mTOR信号通路诱导胰腺癌细胞自噬  

DPC4 gene induces autophagy of pancreatic cancer cells via mTOR signaling pathway

作　　者：邵丽春 邓国伟 卞晓丽 刘欣 SHAO Lichun;DENG Guowei;BIAN Xiaoli;LIU Xin(Department of Gastroenterology,Air Force Hospital,Northern Theater,Shenyang 110042;Department of Internal Medicine,Beihang Clinic,Northern Theater General Hospital;Jinzhou Medical University,China)

机构地区：[1]北部战区空军医院消化内科,辽宁沈阳110042 [2]北部战区总医院北空门诊部内科 [3]锦州医科大学

出　　处：《胃肠病学和肝病学杂志》2019年第12期1403-1406,共4页Chinese Journal of Gastroenterology and Hepatology

基　　金：辽宁省自然基金(201602758)

摘　　要：目的验证过表达DPC4基因对胰腺癌细胞增殖侵袭的抑制作用,探讨mTOR信号通路对其激活自噬的调控作用。方法构建DPC4过表达载体,转染胰腺癌JF305细胞,CCK-8、Transwell检测其对胰腺癌JF305细胞的增殖侵袭能力,透射电镜观察自噬小体,Western blotting法检测自噬相关蛋白Beclin-1、LC3-Ⅱ/Ⅰ、mTOR、p-mTOR、4EBP1、p-4EBP1的表达。结果过表达DPC4可以抑制胰腺癌细胞增殖和侵袭;激活自噬,电镜下DPC4过表达细胞中自噬颗粒明显增多;自噬相关蛋白Beclin-1和LC3-Ⅱ/Ⅰ在过表达DPC4的JF305细胞中表达升高,同时下调p-mTOR和p-4EBP1的表达水平。结论DPC4基因可以抑制胰腺癌细胞增殖和侵袭能力,其作用机制与抑制mTOR信号通路、激活自噬相关。Objective To verify the inhibitory effect of overexpressing DPC4 gene on proliferation and invasion of pancreatic cancer cells,and to explore the regulation of mTOR signaling pathway on its activation of autophagy.Methods The DPC4 overexpression vector was constructed and transfected into pancreatic cancer JF305 cells.The proliferation and invasion ability of pancreatic cancer JF305 cells were detected by CCK-8 and Transwell.The autophagosomes were observed by transmission electron microscopy.The autophagy-related proteins Beclin-1,LC3-Ⅱ/Ⅰ,mTOR,p-mTOR,4EBP1,p-4EBP1 were detected by Western blotting.Results Overexpression of DPC4 could inhibit the proliferation and invasion of pancreatic cancer cells;autophagy was activated,autophagy particles were significantly increased in DPC4 overexpressing cells under electron microscope;autophagy-related proteins Beclin-1 and LC3-Ⅱ/Ⅰwere increased in overexpressing DPC4 of JF305 cells,while the expressions of p-mTOR and p-4EBP1 were down-regulated.Conclusion DPC4 gene can inhibit the proliferation and invasion of pancreatic cancer cells,and its mechanism is related to inhibition of mTOR signaling pathway and activation of autophagy.

关 键 词：DPC4基因 人胰腺癌细胞系JF305 自噬 增殖 侵袭 

分 类 号：R735.[医药卫生—肿瘤]