title: Tetrandrine inhibits migration and invasion of human renal cell carcinoma by regulating Akt/NF-κB/MMP-9 signaling.
abstract: 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.
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China.|Department of Science and Technology, Jinzhou Medical University, Jinzhou, PR China.
authors.forename: Shurui
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China.
authors.forename: Yizeng
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China.
authors.forename: Xinyang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China.
authors.forename: Dalin
authors.initials: D
authors.lastname: He
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D044182:Benzylisoquinolines / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; D016328:NF-kappa B; C009438:tetrandrine; D019869:Phosphatidylinositol 3-Kinases; D064413:3-Phosphoinositide-Dependent Protein Kinases; C578562:PDPK1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D020780:Matrix Metalloproteinase 9