Association between apoptosis induced in hepatoblastoma HepG2 cells by Cdk7 silencing and decreased pRb and Cdk2 phosphorylation / 中国药理学通报

ABSTRACT

Aim: To evaluate the effect of Cdk7 silencing on the cell cycle control, the phosphorylation level changes of Cdk2 and pRb in human hepatoblastoma HepG2 cell culture in vitro, and to validate Cdk7 as a novel target for anticancer therapeutics. Method: Levels of Cdk7 and the phosphorylation levels of Cdk2 and pRb were measured by Western-blotting. DNA contents, cell cycle and apoptosis induced by Cdk7 silencing were analyzed by flow cytometry and ultrastructural changes of cells were observed with transmission electron microscopy. Result The phosphorylation levels of pRb and Cdk2 and the levels of Cdk7 decreased in a concentration-dependent manner when the concentration was above 100 nmol·L-1. Indice of cells arrested in G0/G 1 phases and apoptotic cells increased in a dosage-and time-dependent manner, the difference was significant between Cdk7 ASODN and the sense control (P < 0.01); Characteristic apoptosis in Cdk7 ASODN treated groups were obvious under the transmission electron microscopy. Conclusion: Bioactivities and phosphorylation levels of pRb and Cdk2 decreased after Cdk7 silencing and thus induced obvious G0/G1 phases arrest and apoptosis in HepG2 cell culture in vitro, it is feasible to consider Cdk7 as a novel target for anticancer therapeutics.