DPC4基因抑制PI3K/AKT/mTOR信号通路调控胰腺癌细胞增殖、侵袭及上皮间质转化  

DPC4 gene inhibits PI3K/AKT/mTOR signaling pathway and regulates pancreatic cancer cell proliferation,invasion and epithelial-mesenchymal transition

作　　者：邓国伟 任丽楠 王孟岩 于环宇 邵丽春 DENG Guo-wei;REN Li-nan;WANG Meng-yan;YU Huan-yu;SHAO Li-chun(Department of Internal Medicine,Beihang Clinic,Northern Theater General Hospital,Shenyang 110001;Department of Gastroenterology,General Hospital of Northern Theater,Liaoning,Shenyang 110016;Department of Gastroenterology,Air Force Hospital,Northern Theater,Shenyang 110042,China)

机构地区：[1]北部战区总医院北空门诊部内科,沈阳110001 [2]北部战区总医院消化内科,沈阳110016 [3]北部战区空军医院消化内科,沈阳110042

出　　处：《解剖科学进展》2020年第5期567-569,574,共4页Progress of Anatomical Sciences

基　　金：辽宁省自然科学基金(201602758)。

摘　　要：目的观察DPC4基因对人胰腺癌细胞增殖、侵袭及上皮间质转化(EMT)的影响,探讨PI3K/AKT/mTOR信号通路在其中的作用。方法建立稳转DPC4基因的胰腺癌JF305细胞;取稳转细胞系和正常JF305细胞,CCK8方法观察细胞增殖能力变化;Western blot检测PI3K、P-PI3K、Akt、p-AKT、mTOR、pmTOR及EMT相关标志物(E-cadherin、Vimentin、N-cadherin、Snail)的表达,Transwell检测细胞侵袭能力变化;裸鼠移植瘤实验观察DPC4基因对肿瘤的增殖影响。结果稳转DPC4基因的胰腺癌细胞增殖能力降低,侵袭能力下降,接种稳转DPC4基因的JF305细胞抑制荷瘤小鼠肿瘤生长,E-cadherin蛋白表达水平上调,而Snail、vimentin和N-cadherin蛋白表达水平降低,且PI3K/Akt信号通路受到抑制,p-PI3K,p-Akt、p-mTOR表达水平降低(P<0.05)。结论DPC4基因抑制胰腺癌细胞增殖和侵袭能力,与PI3K/Akt/mTOR信号通路调控EMT相关。Objective To observe the effects of DPC4 gene on tthe proliferation,invasion and epithelialmesenchymal transition(EMT)of human pancreatic cancer cells via the regulation of PI3 K/AKT/mTOR signaling pathway.Methods DPC4 overexpression vector was constructed and transfected into pancreatic cancer JF305 cells.CCK8 was used to observe cell proliferation,Transwell assay was used to determin cell invasion ability;nude mice transplanted tumor was used to observe the effect of DPC4 gene on tumor proliferation.The expression of PI3 K,P-PI3 K,Akt,P-AKT,mTOR,pmTOR and EMT related markers(E-cadherin,Vimentin,N-cadherin,Snail)was detected by Western blot.Results Overexpression of DPC4 inhibited the proliferation of the cells,reduced invasion and migration of the cells,inhibited tumor growth in tumor-bearing mice,up-regulated the expression level of E-cadherin protein,and decreased the expression levels of Snail,vimentin and N-cadherin proteins.In addition,PI3 K/Akt signaling pathway was inhibited and the expression level of p-PI3 K,p-Akt and p-mTOR was decreased,while DPC4 gene was overexpressed.Conclusion DPC4 gene inhibits the proliferation and invasion of pancreatic cancer cells,which is related to the regulation of EMT via PI3 K/Akt/mTOR signaling pathway.

关 键 词：DPC4基因 胰腺癌 PI3K/Akt/mTOR信号通路 上皮间质转化 

分 类 号：R735.9[医药卫生—肿瘤]