Hui Hua1, Yu Zhu2, Yu-He Song3. 1. Zhejiang Pharmaceutical College, No. 888 East Section, Yinxian Road, Higher Education Park (South), Ningbo, Zhejiang Province, China. Electronic address: 176504151@qq.com. 2. College of Pharmacy and Chemistry & Chemical Engineering, Taizhou University, Taizhou, Jiangsu, China. Electronic address: zhuyu0905@sohu.com. 3. College of Pharmacy and Chemistry & Chemical Engineering, Taizhou University, Taizhou, Jiangsu, China. Electronic address: songcrane@163.com.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Alex J Eustace; Bryan T Hennessy; Sean P Kennedy; Michael O'Neill; Darren Cunningham; Patrick G Morris; Sinead Toomey; Carmen Blanco-Aparicio; Sonia Martinez; Joaquin Pastor Journal: Oncogene Date: 2020-02-10 Impact factor: 8.756