Anticancer effect of SN-38 combine d with sorafenib on hepatocellular carcinoma in vitro and its mechanism
10.3785/j.issn.1008-9292.2015.09.03
- VernacularTitle:SN-38与索拉非尼联合应用体外抗肝癌效果及其机制
- Author:
Li XU
1
;
Yuan-Run ZHU
;
Jian CHEN
;
Xiao-Chun YANG
;
Pei-Hua LUO
Author Information
1. 浙江大学药学院
- Keywords:
Key words] Liver neoplasms/drug therapy;
Carcinoma,hepatocellular/pathology;
Benzenesulfonates/therapeutic use;
Camptothecin/analogs&derivatives;
Camptothecin/therapeutic use;
Drug therapy,combination;
Apoptosis;
Genes,p53
- From:
Journal of Zhejiang University. Medical sciences
2015;(5):486-492
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the anticancer effect and its mechanism of SN-38 combined with sorafenib on hepatocellular cancer cell lines HepG-2 and BEL-7402 . Methods: SRB colorimetry was employed to measure the viability of HepG-2 and BEL-7402 cells after the treatment of SN-38 with sorafenib .Propidium iodide flow cytometric assay and DAPI staining were used to evaluate the apoptosis of HCC cells. Western blotting was conducted to detect the expression level of apoptosis-related and DNA damage-related proteins .Results: SRB colorimetry showed the synergistic anticancer activities of SN-38 combined with sorafenib , with a combination index of <0.9.The apoptotic rates of HepG-2 cells in control, 60 nmol/L SN-38, 2.5 μmol/L sorafenib and combination groups were 4.25%±2.45%, 28.95%±10.75%, 3.49%±2.49% and 53.19%±11.21%, respectively ( P <0 .05 ) .Western blotting showed that the combination of these two drugs increased the enzymolysis of PARP , Caspase-8 and Caspase-3 , and promoted the expression levels of p53 , p21 andγ-H2 AX significantly .Conclusion:SN-38 and sorafenib have synergistic anticancer activity on hepatocellular carcinoma cells in vitro with the augmentation of apoptosis .
