The current study focused on the role of Ku70, a DNA-dependent protein kinase (DNA-PK) complex protein, in pancreatic cancer cell resistance to gemcitabine. In both established cell lines (Mia-PaCa-2 and PANC-1) and primary human pancreatic cancer cells, shRNA/siRNA-mediated knockdown of Ku70 significantly sensitized gemcitabine-induced cell death and proliferation inhibition. Meanwhile, gemcitabine-induced DNA damage and subsequent pancreatic cancer cell apoptosis were also potentiated with Ku70 knockdown. On the other hand, exogenous overexpression of Ku70 in Mia-PaCa-2 cells suppressed gemcitabine-induced DNA damage and subsequent cell apoptosis. In a severe combined immune deficient (SCID) mice Mia-PaCa-2 xenograft model, gemcitabine-induced anti-tumor activity was remarkably pontificated when combined with Ku70 shRNA knockdown in the xenografts. The results of this preclinical study imply that Ku70 might be a primary resistance factor of gemcitabine, and Ku70 silence could significantly chemo-sensitize gemcitabine in pancreatic cancer cells. (C) 2017 Elsevier Inc. All rights reserved.
第一作者机构：[1]Shanghai Jiao Tong Univ, Sch Med, Shanghai Tongren Hosp, Dept Gastroenterol, 1111 Xianxia St, Shanghai 200336, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Shanghai Jiao Tong Univ, Sch Med, Shanghai Tongren Hosp, Dept Gastroenterol, 1111 Xianxia St, Shanghai 200336, Peoples R China[*1]Department of Gastroenterology, Shanghai Tongren Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, 1111 Xianxia Street, Shanghai, 200336, China
推荐引用方式(GB/T 7714)：
Ma Jiali,Hui Pingping,Meng Wenying,et al.Ku70 inhibits gemcitabine-induced DNA damage and pancreatic cancer cell apoptosis[J].BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.2017,484(4):746-752.doi:10.1016/j.bbrc.2017.01.146.
APA：
Ma, Jiali,Hui, Pingping,Meng, Wenying,Wang, Na&Xiang, Shihao.(2017).Ku70 inhibits gemcitabine-induced DNA damage and pancreatic cancer cell apoptosis.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,484,(4)
MLA：
Ma, Jiali,et al."Ku70 inhibits gemcitabine-induced DNA damage and pancreatic cancer cell apoptosis".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 484..4(2017):746-752
