Corosolic Acid Inhibits Hepatocellular Carcinoma Cell Migration by Targeting the VEGFR2/Src/FAK Pathway.
Corosolic Acid Inhibits Hepatocellular Carcinoma Cell Migration by Targeting the VEGFR2/Src/FAK Pathway.
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DOI：
10.1371/journal.pone.0126725
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Lin JY
中科院分区：
文献类型：
--
作者：
Ku CY;Wang YR;Lin HY;Lu SC;Lin JY
抑制VEGFR2活性已被提出作为肝细胞癌（HCC）临床治疗的重要策略。在本研究中，我们发现猕猴桃（Actinidia chinensis）根中含有的corosolic acid （CA）对HCC细胞具有显著的抗癌作用。我们发现CA通过直接与ATP结合袋相互作用抑制VEGFR2激酶活性。CA下调VEGFR2/Src/FAK/cdc42轴，随后在体外降低F-actin的形成和迁移活性。在体内模型中，CA对肿瘤生长表现出有效剂量（5 mg/kg/天）。我们进一步证明CA在广泛的浓度范围内与索拉非尼具有协同效应。总之，本研究阐明了CA对HCC细胞的作用及其分子机制，提示CA可能是侵袭性HCC患者的一种治疗或辅助策略。
Inhibition of VEGFR2 activity has been proposed as an important strategy for the clinical treatment of hepatocellular carcinoma (HCC). In this study, we identified corosolic acid (CA), which exists in the root of Actinidia chinensis, as having a significant anti-cancer effect on HCC cells. We found that CA inhibits VEGFR2 kinase activity by directly interacting with the ATP binding pocket. CA down-regulates the VEGFR2/Src/FAK/cdc42 axis, subsequently decreasing F-actin formation and migratory activity in vitro. In an in vivo model, CA exhibited an effective dose (5 mg/kg/day) on tumor growth. We further demonstrate that CA has a synergistic effect with sorafenib within a wide range of concentrations. In conclusion, this research elucidates the effects and molecular mechanism for CA on HCC cells and suggests that CA could be a therapeutic or adjuvant strategy for patients with aggressive HCC.