The inhibitory effect of Withaferin A on the growth of orthotopic xenograft tumor of hepatocellular carcinoma in nude mice and the mechanism
10.3760/cma.j.issn.1008-1372.2017.12.012
- VernacularTitle:醉茄素A对裸鼠人肝癌原位移植瘤的抑制作用及机制研究
- Author:
Xianmin MU
1
;
Wei SHI
;
Yue XU
;
Shi HU
;
Jing YANG
;
Che XU
;
Chen ZHANG
;
Jinshun PAN
;
Biao GENG
;
Qiang YOU
Author Information
1. 210011,南京医科大学第二附属医院生物治疗中心
- Keywords:
Withanolides/PD;
Liver neoplasms/ZD;
Cell proliferation/DE;
Neovascularization;
pathologic
- From:
Journal of Chinese Physician
2017;19(12):1800-1803,1806
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the inhibitory effect of Withaferin A ( WFA) on the growth of orthotopic xenograft tumor of hepatocellular carcinoma in nude mice and the mechanism of its antitumoral effect. Methods For in vivo model, anti-tumor efficacy of Withaferin A was evaluated in nude mice mod-els of human liver cancer orthotopic xenograft. The nude mice were randomly divided into model group, Sunitinib group,and Withaferin A groups [6, 3 mg/(kg·d)]. All mice were given intraperitoneal injec-tion for 14 days. Tumor volume and tumor weight were observed. Antiangiogenic effects were assessed in vi-vo by the tumor inhibition rate and microvessel density. Quantitative polymerase chain reaction ( QPCR) as-say was used to detect the mRNA expression of vascular endothelial growth factor ( VEGF) , basic fibroblast growth factor (bFGF), angiopoietin-2 (Ang-2), vascular endothelial growth factor receptor 2 (VEGFR2) from tumor tissues. For in vitro experiments, the cell count kit 8 ( CCK8 ) assay was used to detect the effect of Withaferin A on HepG2 cells proliferation. QPCR assay and enzyme-linked immunosorbent assay ( ELISA) were used to detect the mRNA expression of VEGF. Results Compared to the model group, the high-dose Withaferin A group and the Sunitinib group had a significantly lower tumor weight (P<0. 05). The tumor inhibition rate was 42. 69％ in the high-dose Withaferin A group, 20. 22％ in the low-dose With-aferin A group, and 49. 43％ in the Sunitinib group. The growth of HepG2 cells was significantly inhibited by different concentrations of Withaferin A,and the 50％ concentration of inhibition ( IC50 ) of Withaferin A were (2. 64 ± 0. 18)μmol/L at 24 h. Withaferin A (6,3 μmol/L) could inhibit the protein and mRNA ex-pression of VEGF ( P<0. 05 ) . Conclusions Withaferin A significantly reduces the growth of orthotopic xenograft tumor of hepatocellular carcinoma in nude mice via antiangiogenic effect. Downregulation of the protein and mRNA expression of VEGF by WFA may be one mechanism of its anti-liver cancer effect.
