Mechanism of active ingredients of Venenum Bufonis in down-regulating expression of aurora kinase and promoting cell cycle arrest in human liver cancer HepG2 cells / 中草药

ABSTRACT

Objective To investigate the function of aurora kinase (AURK) in liver cancer and the mechanism of cinobufagin and bufalin-induced liver cancer HepG2 cells growth inhibition by down-regulating AURK family. Methods Kaplan-Meier survival method analyzed the relationship between mRNA expression levels of AURKA and AURKB and survival periods. The viability and cell cycle of HepG2 cells were detected by MTT method and flow cytometry. Western blotting analyzed the expression levels of spindle-associated protein AURKA, AURKB, TPX2, SMC2, TOP2A, and cyclin-dependent kinase CDK1. Results Kaplan-Meier survival analysis presented a significantly negative correlation between mRNA expression levels of AURKA and AURKB and survival periods. Cinobufagin and bufalin inhibited the growth of HepG2 cells in a time- and dose-dependent manner, and induced the cell cycle G2/M phase arrest. They all down-regulated the expression of AURKA, AURKB, TPX2, SMC2, TOP2A, and CDK1 (P < 0.05). Conclusion There is a significantly negative correlation between mRNA expression levels of AURKA and AURKB and survival periods. Cinobufagin and bufalin could induce HepG2 cells growth inhibition and cell cycle arrest by down-regulating the expression of AURKA and AURKB and other mitosis-regulating proteins.