Development of molecular medicine for hepatocellular carcinoma targeting on hepatic stellate cells

为了开发针对肝癌和肝星状细胞相互作用的新策略，我们研究了相互作用，即血管紧张素II(AngII)-去整合素和金属蛋白酶结构域(ADAM)-表皮生长因子受体(EGFR)。在两种细胞(肝细胞癌和肝星状细胞)中，应用血管紧张素转换酶II均可增强细胞的增殖/侵袭活性。血管紧张素受体阻滞剂(ARB)和/或ADAM抑制剂(TAPI2)可抑制这种反式激活(AngII-ADAM-EGFR)。这些结果提示ARB和/或ADAM抑制剂将成为治疗肝癌和肝纤维化的新药。

For the development of new strategy targeting on the interaction between hepatoceullar carcinoma (HCC) and hepatic stellate cells, we investigated the cross-talk ; namely angiotensin II (AngII)-a disintegrin and metalloprotease domain (ADAM)- epidermal growth factor receptor (EGFR). In both cell types (HCC and HSC), the increase of proliferation/invasion activities by the administration of Ang II was observed. The transactivation (AngII-ADAM-EGFR) was inhibited by angiotensin receptor blocker (ARB) and/or ADAM inhior (TAPI2). These results suggested ARB and/or ADAM inhibitor will be new drugs for the treatment in both HCC and liver fibrosis.