title: PP242 suppresses bladder cancer cell proliferation and migration through deactivating the mammalian target of rapamycin complex 2/AKT1 signaling pathway.
abstract: While most cancer types are resistant to mammalian target of rapamycin complex 1 (mTORC1) inhibitor rapamycin, recent studies have identified mTORC2 as an important prospective therapeutic target for cancer. The present study assessed the effects of mTORC2 inhibitor PP242 on the proliferation and migration of bladder cancer cells by using Cell Counting Kit‑8, 5‑ethynyl‑2'‑deoxyuridine incorporation, wound healing and Transwell assays. Furthermore, the phosphorylation status of downstream signaling proteins of mTORC1 and mTORC2 was assessed using western blot analysis. The results demonstrated that PP242 concentration‑dependently inhibited the proliferation of bladder cancer cells. Simultaneously, the migration ability of bladder cancer cells was suppressed by PP242. In addition, PP242 markedly restrained the phosphorylation of AKT1 and mTORC2, while the phosphorylation status of S6K1 and mTORC1 was not affected. These results suggested that PP242 exerts potent inhibitory effects on bladder cancer cells by modulating the activity of the mTORC2/AKT1 pathway.
authors.affiliation: Department of Urology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110022, P.R. China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Urology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Chuize
authors.initials: C
authors.lastname: Kong
authors.affiliation: Department of Urology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Daxin
authors.initials: D
authors.lastname: Gong
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011687:Purines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D007211:Indoles; D046912:Multiprotein Complexes; D011687:Purines; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C572919:PP242