title: Rapamycin inhibits the invasive ability of thyroid cancer cells by down-regulating the expression of VEGF-C in vitro.
abstract: The aim of this study was to observe the effects of rapamycin on proliferation, apoptosis and invasion of SW579 in vitro. The proliferation and apoptosis of SW579 cells were detected by methyl thiazolyl tetrazolium and flow cytometry. Transwell assay was used to observe the changes of invasive ability of SW579 cells after being treated with rapamycin. The effects of rapamycin on the expression of mammalian target of rapamycin (mTOR) signalling and vascular endothelial growth factor C (VEGF-C) were observed by Western blot. The inhibition and apoptosis rates increased obviously when the concentration of rapamycin was 20 nm. When the rapamycin concentration was 10 nm, the invasive ability of SW579 cells changed significantly than when it was 5 nm. Our data showed that when the concentrations of rapamycin were over 20 nm, the expression of mTOR and p70S6K decreased significantly, and the expression of PTEN increased notably. There were no remarkable variations observed when we detected the expression of Akt. We found the expression of VEGF-C was high in SW579 cells and decreased slightly when the cells were treated with 5 nm rapamycin. When the concentration of rapamycin was over 5 nm, significant changes were observed. Rapamycin could inhibit the proliferation and induce the apoptosis of human thyroid cancer cells in vitro by mTOR inhibition. No obvious changes observed in the expression of AKT indicated that there might be a feedback loop effect by the mTOR inhibition induced by rapamycin. Rapamycin could inhibit the invasive ability of SW579 cells by down-regulating the expression of VEGF-C.
authors.affiliation: Department of Head and Neck Surgery, the Third Affiliated Hospital, Harbin Medical University, Harbin 150081, Heilongjiang China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Feng
authors.forename: Shenshan
authors.initials: S
authors.lastname: Jia
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis*
chemical_list: D000970:Antineoplastic Agents; D042582:Vascular Endothelial Growth Factor C; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus