title: Tetrandrine suppresses metastatic phenotype of prostate cancer cells by regulating Akt/mTOR/MMP-9 signaling pathway.
abstract: Tetrandrine (TET), a bisbenzylisoquinoline alkaloid found in traditional Chinese medicines, exerts anticancer activity in vitro and in vivo. However, its potential role in the prostate cancer metastatic process has not yet been elucidated. Thus, we investigated the inhibition effect of tetrandrine on prostate cancer migration and invasion and the corresponding molecular basis underlying its anticancer activity. Cell migration and invasion were determined using the Transwell chamber model. The protein expression of Akt, phosphorylated Akt, the mammalian target of rapamycin (mTOR), phosphorylated mTOR and matrix metalloproteinases 9 (MMP-9) was detected by western blot in the presence or absence of tetrandrine or in the group tetrandrine combination with LY294002 (inhibitor of Akt) and rapamycin (inhibitor of mTOR). Our studies showed that excluding the effect of tetrandrine on cell proliferation, tetrandrine significantly inhibited cell migration and invasion in prostate cancer DU145 and PC3 cells. Furthermore, tetrandrine decreased the protein levels of p-Akt, p-mTOR, and MMP-9. While the inhibition of Akt or mTOR by the respective inhibitors could potentiate this effect of tetrandrine on prostate cancer cells, the studies indicate that tetrandrine inhibits the metastasis process by negatively regulating the Akt/mTOR/MMP-9 signaling pathway. These results suggest that tetrandrine might serve as a potential metastasis suppressor to treat cancer cells that have escaped surgical removal or that have disseminated widely.
authors.affiliation: Department of Cadiovascular Sugery, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Kou
authors.affiliation: Department of Urology, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Burn and Plastic Surgery, Xi'an Central Hospital, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cadiovascular Sugery, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Jianjie
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Cadiovascular Sugery, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Cadiovascular Sugery, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cadiovascular Sugery, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Suochun
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Cadiovascular Sugery, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Haichen
authors.initials: H
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D044182:Benzylisoquinolines; C009438:tetrandrine; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9