KLF4 silencing and doxorubicin-induced DNA damage inhibit the growth of hepatocellular carcinoma HepG2 cells
YU Zhaoyang1,2， LI Juan1， LI Hua2， FEI Dong2， XUE Huiying1
1.Department of Pharmacy， Tongji Hospital， Tongji Medical College， Huazhong University of Science and Technology， Wuhan 430030， China；2. School of Pharmacy， Tongji Medical College， Huazhong University of Science and Technology， Wuhan 430030， China
Abstract：In this paper， the effect of KLF4 silencing and DNA damage induced by different concentrations of doxorubicin on proliferation and apoptosis of HepG2 cells and its related mechanism were investigated. RNA interference technique was applied to siRNA transfection of HepG2 cells to silence KLF4 genes. And the effect of KLF4 on HepG2 cell proliferation treated with cytostatic concentration and cytotoxic concentration on doxorubicin were detected by MTT assay before and after KLF4 knockdown. The effect of KLF4 on HepG2 cell cycle was analyzed by flow cytometry before and after KLF4 silence. The expression of KLF4 protein and cell cycle related protein in HepG2 cells was examined by western blot before and after transfection. Western blot results showed that high concentration of doxorubicin promoted the expression of KLF4. Moreover， low concentrations of doxorubicin caused cells arrest in G2/M phase， while high concentrations of doxorubicin induced cell apoptosis (19.31%). After silencing KLF4， the MTT results showed that cell growth decreased. Cells treated with low concentration of doxorubicin， exhibited more apoptosis with increasing time. After treatment with high concentration of doxorubicin， cell viability reduced significantly， and number of apoptotic cells increased (28.89%). Moreover， the expression of p53 and p21 were promoted by low concentration of doxorubicin while inhibited by high concentration of doxorubicin. Doxorubicin-mediated DNA damage enhanced the expression of KLF4. In summary， KLF4 might inhibit the proliferation and promote apoptosis of human hepatoma cancer cells through p21 signal pathway and DNA damage-activated p53 signal pathway， suggesting its important function in hepatoma cancer HepG2 cells.
2019, Vol. 53 
