Abstract: Objective Cellular senescence as one of the important steps against tumor is observed in many cancer patients
receiving chemotherapy and is related to chemotherapeutic response. To investigate the effect of cisplatin on hepatocellular
carcinoma, we treated HepG2 cells exhibiting wild-type TP53 with gradient concentrations of cisplatin. Methods The
inhibitory effects of cisplatin on human hepatoma HepG2 cells were detected by MTT assay and colony formation test. The
changes in cell cycle were analyzed by flow cytometry, and cellular senescence was detected with senescence associated
β-galactosidase (SA β-gal) staining. The relative mRNA expression levels of TP53, P21 and P19 was estimated using
semi-quantitative real-time RT-PCR, and the protein expressions of P53 and P21 were detected using Western blotting. Results
Cisplatin induced irreversible proliferation inhibition and G1 phase arrest of HepG2 cells. Elevated levels of
senescence-associated β-galactosidase was observed in HepG2 cells exposed to low doses of cisplatin. P19 expression
immediately increased following cisplatin exposure and reached the maximum level at 48 h, followed then by a rapid decrease
to the baseline level, whereas the expressions levels of TP53 and P21 mRNA increased continuously. Western blotting
confirmed P53 and P21 expression changes similar to their mRNA expressions during cisplatin-induced cellular senescence in
HepG2 cells. Conclusion Our results revealed a functional link between cisplatin and hepatocellular senescence. Cellular
senescence induced by cisplatin as a stabile senescent cellular model can be used for further research.