Zhejiang Pharmaceutical College, No. 888 East Section, Yinxian Road, Higher Education Park (South), Ningbo, Zhejiang Province, China.
College of Pharmacy and Chemistry & Chemical Engineering, Taizhou University, Taizhou, Jiangsu, China.
Biomed Pharmacother. 2018 May;101:115-122. doi: 10.1016/j.biopha.2018.02.031. Epub 2018 Feb 23.
Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related mortality with poor prognosis and treatment. More effective strategies should be studied in HCC.
After treated with ruscogenin, the cell proliferation was assessed by CCK-8 method. Cell migration and invasion were estimated using wound healing and transwell assays. Pathological changes of lung tissue were observed by HE staining and IHC methods. MMP-2, MMP-9, uPA, VEGF and HIF-1α levels were measured using ELISA, RT-qPCR and WB tests. PI3K/Akt/mTOR pathway related molecules were detected using WB analysis.
The results indicated the hypotoxicity of ruscogenin. Meanwhile, ruscogenin showed obvious interruption on the cancer cell migration and invasion, and inhibition on the metastatic foci in pulmonary tissue. Significantly, ruscogenin decreased the levels of MMP-2, MMP-9, uPA, VEGF and HIF-1α, down-regulated the phosphorylation of Akt, mTOR.
The present study indicated a novel use of ruscogenin in suppressing HCC metastasis by reducing the expression of MMP-2, MMP-9, uPA, VEGF and HIF-1α via regulating the PI3K/Akt/mTOR signaling pathway.
肝细胞癌（HCC）是癌症相关死亡的第三大主要原因，预后和治疗效果较差。应该研究更有效的策略来治疗 HCC。
用美洲大蠊素处理细胞后，通过 CCK-8 法评估细胞增殖。通过划痕愈合和 Transwell 测定法评估细胞迁移和侵袭。通过 HE 染色和 IHC 方法观察肺组织的病理变化。通过 ELISA、RT-qPCR 和 WB 试验测量 MMP-2、MMP-9、uPA、VEGF 和 HIF-1α 水平。通过 WB 分析检测 PI3K/Akt/mTOR 通路相关分子。
结果表明美洲大蠊素具有低毒性。同时，美洲大蠊素对癌细胞迁移和侵袭有明显的阻断作用，并抑制肺组织中的转移灶。值得注意的是，美洲大蠊素降低了 MMP-2、MMP-9、uPA、VEGF 和 HIF-1α 的水平，下调了 Akt、mTOR 的磷酸化。
本研究表明美洲大蠊素通过调节 PI3K/Akt/mTOR 信号通路降低 MMP-2、MMP-9、uPA、VEGF 和 HIF-1α 的表达，从而具有抑制 HCC 转移的新用途。
