Ku70 inhibits gemcitabine-induced DNA damage and pancreatic cancer cell apoptosis.

Jiali Ma, Pingping Hui, Wenying Meng, Na Wang, Shihao Xiang

Biochemical and biophysical research communications 2017 Mar 18

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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. Copyright © 2017 Elsevier Inc. All rights reserved.

Citation

Jiali Ma, Pingping Hui, Wenying Meng, Na Wang, Shihao Xiang. Ku70 inhibits gemcitabine-induced DNA damage and pancreatic cancer cell apoptosis. Biochemical and biophysical research communications. 2017 Mar 18;484(4):746-752