Journal Article

Tetrandrine inhibits migration and invasion of human renal cell carcinoma by regulating Akt/NF-κB/MMP-9 signaling

Fan, Yizeng, Liu, Wei, Zeng, Jin, Wang, Ke, Ma, Jianbin, Chen, Jiaqi, He, Dalin, Li, Lei, Chen, Shurui, Wang, Xinyang

2017

Overview

Renal cell carcinoma (RCC) is known as one of the most lethal malignancies in the urological system because of its high incidence of metastasis. Tetrandrine (Tet), a traditional Chinese herbal medicine, exerts a potent anti-cancer effect in a variety of cancer cells. However, the anti-metastatic effect of Tet and its possible mechanism in RCC is still unclear. The present study revealed that Tet significantly suppressed the migration and invasion of RCC 786-O and 769-P cells in vitro. Mechanistically, the protein levels of matrix metalloproteinases 9 (MMP-9), phosphorylated PI3K, PDK1, Akt and NF-κB were markedly reduced after Tet treatment. Moreover, co-treatment with LY294002 (PI3K inhibitor) could further enhance the Tet-inhibited migration and invasion, and the NF-κB and MMP-9 protein levels were further decreased. Similar results were observed after PDTC (NF-κB inhibitor) co-treatment. Conversely, SC79, an Akt activator, could partially reverse the anti-metastatic effects of Tet, accompanied by the restoration of NF-κB and MMP-9 protein levels. In conclusion, the current results indicated that Tet inhibited migration and invasion of RCC partially by regulating Akt/NF-κB/MMP-9 signaling pathway, suggesting that Tet may be a potential therapeutic candidate against metastatic RCC.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 1-Phosphatidylinositol 3-kinase / 3-Phosphoinositide-Dependent Protein Kinases - metabolism / AKT protein / Angiogenesis / Anticancer properties / Antineoplastic Agents, Phytogenic - pharmacology / Apoptosis / Benzylisoquinolines - pharmacology / Biology and Life Sciences / Bladder cancer / Breast cancer / Cancer / Cancer therapies / Carcinoma, Renal Cell - drug therapy / Carcinoma, Renal Cell - metabolism / Carcinoma, Renal Cell - pathology / Cell cycle / Cell Line, Tumor / Cell Movement - drug effects / Cell Proliferation - drug effects / Chemotherapy / Gelatinase B / Herbal medicine / Hospitals / Humans / Inhibitors / Kidney cancer / Kidney Neoplasms - drug therapy / Kidney Neoplasms - metabolism / Kidney Neoplasms - pathology / Matrix Metalloproteinase 9 - metabolism / Matrix metalloproteinases / Medicine and Health Sciences / Metastases / Metastasis / Microscopy / NF-kappa B - metabolism / NF-κB protein / Oncology / Phosphatidylinositol 3-Kinases - metabolism / Phosphorylation - drug effects / Prostate cancer / Proto-Oncogene Proteins c-akt - metabolism / Renal cell carcinoma / Research and Analysis Methods / Restoration / Retailing / Signal transduction / Signal Transduction - drug effects / Signaling / Tetrandrine / Urogenital system / Urology