The role and mechanism of low-dose aspirin with IFN-α in inhibiting growth and metastasis of hepatocellular carcinoma
10.3760/cma.j.issn.1007-8118.2012.01.015
- VernacularTitle:小剂量阿司匹林协同干扰素-α抑制肝细胞肝癌生长转移的实验研究
- Author:
Tao LI
;
Xuting ZHI
;
Jianwei ZHOU
;
Zhaoru DONG
;
Hui QU
;
Haihua YU
;
Lu WANG
;
Zhaoyou TANG
- Publication Type:Journal Article
- Keywords:
Hepatocellular carcinoma;
Interferon-α;
Aspirin;
Metastasis
- From:
Chinese Journal of Hepatobiliary Surgery
2012;18(1):50-53
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo study the role and mechanism of low-dose aspirin with IFN-α in inhibiting growth and metastasis of hepatocellular carcinoma (HCC).MethodsMHCC97L cells were cultured and a metastatic model of human HCC was established by orthotopic implantation of histologically intact human HCC tissue into the liver of nude (nu/nu) mice.After administration of different doses of Aspirin and IFN-α for 40 days,the mice bearing xenografts in liver were killed,and the tumor volume and lung metastasis were evaluated.Cell proliferation and MMP-2 activity were measured by MTT and gelatin zymography,respectively.The expressions of VEGF and MMP-2 were measured by western blot and ELISA.ResultsCompared to the control group,there were no significant differences in the high-dose Aspirin [45 mg/(kg · d)] treated group regarding tumor volume [(1.89 ±0.88) cm3 vs (3.12±0.85) cm3,P＞0.05] and incidence of lung metastases (58.3％ vs 66.7％,P＞0.05),but the tumor volume and incidence of lung metastasis were significantly inhibited in the highdose IFN-α group [1.5 × 107/(kg · d)],the high-dose IFN-α combined with high-dose Aspirin group,and the low-dose IFN-α [7.5 × 106 / (kg · d) ] combined with low-dose Aspirin [15 mg/(kg · d] group (P＜0.05).2 mmol/L Aspirin did not inhibit the proliferation of MHCC97 cells (P＞0.05),but inhibited the activities and expressions of MMP-2 and VEGF.Low-dose IFN-α combined with low-dose Aspirin significantly decreased the expressions of MMP-2 and VEGF in nude mice (P＜0.05).ConclusionLow-dose Aspirin combined with low-dose IFN-α significantly inhibited the growth and metastasis of HCC through suppressing the expressions of MMP-2 and VEGF.
