%0 Journal Article
%T 二甲双胍通过激活胰腺癌细胞AMPK通路抑制TGF-β1表达<br>Effect and mechanism of metformin on TGF-β1 expression in pancreatic cancer
%A 段万星
%A 陈 科
%A 薛梦雯
%A 周灿灿
%A 雷建军
%A 徐勤鸿
%A 马清涌
%A 仵 正
%J 西安交通大学学报(医学版)
%D 2019
%R 10.7652/jdyxb201904003
%X 摘要：目的? ?探讨二甲双胍对胰腺癌细胞TGF-β1表达的影响及可能的机制。方法?? 二甲双胍干预胰腺癌细胞株Panc-1及BxPC-3，MTT法检测细胞增殖；Transwell法检测细胞侵袭能力；qRT-PCR、Western blot及免疫荧光法检测细胞中TGF-β1表达，Western blot检测细胞中AMPK/p-AMPK的表达，ELISA法检测细胞培养上清液中TGF-β1的含量。采用基因沉默技术敲除胰腺癌细胞AMPK后，二甲双胍干预，qRT-PCR及Western blot检测TGF-β1的表达情况。结果?? 二甲双胍干预后，Panc-1及BxPC-3细胞AMPK的磷酸化水平明显降低，肿瘤细胞内TGF-β1的表达明显减少(Panc-1：P<0.001；BxPC-3：P<0.001)，敲除肿瘤细胞AMPK可以逆转二甲双胍对TGF-β1的下调作用(P<0.05)。结论?? 二甲双胍可以通过诱导AMPK磷酸化而抑制胰腺癌细胞内TGF-β1的表达。<br>ABSTRACT: Objective??? To investigate the effect of metformin on TGF-β1 expression in pancreatic cancer and further analyze the underlying mechanism. Methods??? After metformin intervention, cell proliferation and invasion ability were detected by MTT assay and Transwell method, respectively. The expression of TGF-β1 in pancreatic cancer cell lines Panc-1 and BxPC-3 was detected by qRT-PCR, Western blot and immunofluorescence. The expression of AMPK/p-AMPK was detected by Western blot; ELISA method was used to measure the content of TGF-β1 in cell supernatant. After silencing AMPK expression in pancreatic cancer cell lines, the cells were treated with metformin and the expression of TGF-β1 was detected by qRT-PCR and Western blot. Results??? The phosphorylation level of AMPK in Panc-1 (P<0.001) and BxPC-3 (P<0.001) cells was significantly decreased after metformin intervention. In addition, the expression of TGF-β1 in tumor cells was significantly decreased. However, the reduced expression of TGF-β1 by metformin was reversed by AMPK silencing in cancer cells (P<0.05). Conclusion??? Metformin can inhibit TGF-β1 expression in pancreatic cancer cells by inducing AMPK phosphorylation
%K 二甲双胍
%K 胰腺癌
%K 转化生长因子-β1
%K 基因沉默
%K 腺苷酸活化蛋白激酶<br>metformin
%K pancreatic cancer
%K transforming growth factor-β1(TGF-β1)
%K gene silencing
%K AMP-activated protein kinase (AMPK)
%U http://yxxb.xjtu.edu.cn//oa/darticle.aspx?type=view&id=201904003