Anticancer effect of SN-38 combined with sorafenib on hepatocellular carcinoma in vitro and its mechanism.
- Author:
Li XU
1
;
Zhu YUAN-RUN
1
;
Chen JIAN
1
;
Yang XIAO-CHUN
1
;
Luo PEI-HUA
1
Author Information
- Publication Type:Journal Article
- MeSH: Apoptosis; Camptothecin; analogs & derivatives; pharmacology; Carcinoma, Hepatocellular; pathology; Caspase 3; metabolism; Caspase 8; metabolism; Cell Line, Tumor; drug effects; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21; metabolism; Histones; metabolism; Humans; Liver Neoplasms; pathology; Niacinamide; analogs & derivatives; pharmacology; Phenylurea Compounds; pharmacology; Poly(ADP-ribose) Polymerases; metabolism; Tumor Suppressor Protein p53; metabolism
- From: Journal of Zhejiang University. Medical sciences 2015;44(5):486-492
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the anticancer effect and its mechanism of SN-38 combined with sorafenib on hepatocellular cancer cell lines HepG-2 and BEL-7402.
METHODSSRB 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.
RESULTSSRB 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, 2.5μmol/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 and γ-H2AX significantly.
CONCLUSIONSN-38 and sorafenib have synergistic anticancer activity on hepatocellular carcinoma cells in vitro with the augmentation of apoptosis.
