Inhibition of epithelial-mesenchymal transition represses metastastic potential of hepatocellular carcinoma enhanced by hepatic arterial occlusion in mice
10.3760/cma.j.issn.1007-631X.2012.02.010
- VernacularTitle:抑制残癌细胞上皮间质转化能降低肝动脉结扎增强的肝癌转移潜能
- Author:
Liang LIU
;
Huaxiang XU
;
Wenquan WANG
;
Zhaoyou TANG
- Publication Type:Journal Article
- Keywords:
Carcinoma,hepatocellular;
Neoplasm metastasis;
Anoxia;
Hepatic arterial occlusion;
Epithelial mesenchymal transition
- From:
Chinese Journal of General Surgery
2012;27(2):123-126
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of inhibiting epithelial mesenchymal transition (EMT) on metastastic potential of hepatocellular carcinoma (HCC) enhanced by hepatic arterial occlusion in mice. Methods Using a metastatic human HCC orthotopic nude mice model (MHCC97),the effects of hepatic artery ligation (HAL) alone,combination of HAL and phosphatidylinositol 3-kinase (PI3K)inhibitor LY294002,or combination of HAL and interferon-α (IFN-α) on the growth of planted human HCC cells and pulmonary metastasis were evaluated,respectively.The cells and tumor tissues specimens were analyzed through expression of Akt,p-Akt,E-cadhein,N-cadherin and Twist. Results HAL inhibits tumor growth (2002.97 ± 331.28 ) mm3 vs.( 3921.23 ± 786.21 ) mm3,t =4.052,P ＜ 0.01 ),while promoting pulmonary metastatsis ( 10/12 vs.4/12,P ＜ 0.05).HAL combined with LY294002 represses significantly enhanced pulmonary metastasis rate by HAL alone (0/6 vs.6/6,P ＜ 0.01 ).Moderate-dose IFN-α (7.5 × 106 U/kg) combined with HAL failed to further reduce tumor volume compared with that of HAL alone,but inhibited markedly pulmonary metastasis (2/6 vs.6/6,P ＜ 0.05 ).The augmented level of N-cadherin and Twist in tumor tissues due to HAL reduced by LY294002 or 7.5 × 106 U/kg IFN-α.The arrest of EMT by LY294002 or IFN-α in HAL-treated xenografts was further demonstrated by the in vitro response of hypoxic cells to both agents. Conclusions Inhibition of EMT in HCC cells could repress enhanced metastastic potential due to hepatic arterial occlusion.
