Feng Long-Hai, Sun Hui-Chuan, Zhu Xiao-Dong, Zhang Shi-Zhe, Li Xiao-Long, Li Kang-Shuai, Liu Xue-Feng, Lei Ming, Li Yan, Tang Zhao-You
Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.
Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
Ann Transl Med. 2021 Feb;9(3):207. doi: 10.21037/atm-20-5293.
The use of angiotensin II inhibitors is associated with a low risk of recurrence and metastasis in hepatocellular carcinoma (HCC) patients. Vascular cell adhesion molecule-1 (VCAM-1) is a key factor in tumor metastasis.
The effects of angiotensin II and irbesartan (an angiotensin II inhibitor) on HCC were explored with a xenograft model, microarray analysis and cell adhesion experiments. The relationship between the expression of VCAM-1 in HCC tissues and prognosis was analyzed with public and our institutional clinical databases. The effects of angiotensin II, irbesartan and VCAM-1 on adhesion and metastasis in HCC were explored with a xenograft model and cell adhesion experiments. The regulatory mechanisms were analyzed by Western blot analysis.
Angiotensin II type 1 receptor and VCAM-1 were expressed in HCC tissues. Irbesartan inhibited HCC growth and metastasis in vivo and weakened the adhesion of HCC cells to endothelial cells, an effect that was enhanced by angiotensin II. VCAM-1 was found to be an independent risk factor for recurrence and survival in HCC patients with microvascular invasion. Angiotensin II upregulated VCAM-1 expression, and this upregulation was inhibited by irbesartan. Angiotensin II enhanced adhesion mainly by promoting the expression of VCAM-1 in HCC cells. Irbesartan inhibited the expression of VCAM-1 by reducing p38/MAPK phosphorylation activated by angiotensin II in HCC cells.
Irbesartan attenuates metastasis by inhibiting angiotensin II-activated VCAM-1 via the p38/MAPK pathway in HCC.
血管紧张素II抑制剂的使用与肝细胞癌（HCC）患者的复发和转移低风险相关。血管细胞粘附分子-1（VCAM-1）是肿瘤转移的关键因素。
采用异种移植模型、微阵列分析和细胞粘附实验，探讨血管紧张素II和厄贝沙坦（一种血管紧张素II抑制剂）对肝癌的影响。利用公共和我们机构的临床数据库分析HCC组织中VCAM-1表达与预后的关系。通过异种移植模型和细胞粘附实验，探讨血管紧张素II、厄贝沙坦和VCAM-1对肝癌粘附和转移的影响。通过蛋白质印迹分析来分析调控机制。
血管紧张素II 1型受体和VCAM-1在HCC组织中表达。厄贝沙坦在体内抑制HCC生长和转移，并减弱HCC细胞与内皮细胞的粘附，血管紧张素II可增强这种作用。发现VCAM-1是微血管侵犯的HCC患者复发和生存的独立危险因素。血管紧张素II上调VCAM-1表达，而这种上调被厄贝沙坦抑制。血管紧张素II主要通过促进HCC细胞中VCAM-1的表达来增强粘附。厄贝沙坦通过降低血管紧张素II激活的HCC细胞中p38/MAPK磷酸化来抑制VCAM-1的表达。
在肝癌中，厄贝沙坦通过p38/MAPK途径抑制血管紧张素II激活的VCAM-1，从而减弱转移。
