Cisplatin induces cell cycle arrest and senescence via upregulating P53 and P21 expression in HepG2 cells
10.3969/j.issn.1673-4254.2013.09.01
- VernacularTitle:顺铂通过调控P53及P21表达水平影响HepG2细胞衰老及周期阻滞
- Author:
Kai QU
1
;
Ting LIN
;
Jichao WEI
;
Fandi MENG
;
Zhixin WANG
;
Zichao HUANG
;
Yong WAN
;
Sidong SONG
;
Sinan LIU
;
Hulin CHANG
;
Yafeng DONG
;
Chang LIU
Author Information
1. 西安交通大学医学院第一附属医院肝胆外科
- Keywords:
cisplatin;
cellular senescence;
hepatocellular carcinoma;
P53;
P21
- From:
Journal of Southern Medical University
2013;(9):1253-1259
- CountryChina
- Language:Chinese
-
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 associatedβ-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.