title: Dual blocking of PI3K and mTOR signaling by NVP-BEZ235 inhibits proliferation in cervical carcinoma cells and enhances therapeutic response.
abstract: NVP-BEZ235 is a novel dual PI3K/mTOR inhibitor that shows dramatic effects on many tumors, but its effects on cervical carcinoma cells are largely unknown. In the present study, we investigated the effects of NVP-BEZ235 on the proliferation and invasion of cervical carcinoma cells in vitro and clarified its mechanism of action. In cellular settings with human cervical carcinoma cell lines, this molecule effectively and specifically blocked dysfunctional PI3K/mTOR pathway activation, suppressed cell growth in a time- and concentration-dependent manner, led to G1 cell cycle arrest, and induced apoptosis. NVP-BEZ235 suppressed HeLa cell invasiveness and metastasis by inhibiting the PI3K/Akt/MMP-2 pathway. We further demonstrated that NVP-BEZ235 treatment in combination with cisplatin or carboplatin induced a synergistic anti-tumoral response in cervical carcinoma cells. These findings suggested that NVP-BEZ235 could regulate growth and invasion of cervical carcinoma cells; thus it may provide a potential therapy for cervical carcinoma.
authors.affiliation: Department of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, China.
authors.forename: Guifang
authors.initials: G
authors.lastname: Xie
authors.affiliation: Department of Pathology, The Second Hospital of Jilin University, Changchun, China.
authors.forename: Zhaoyong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, Changchun, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, China.
authors.forename: Shuya
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, China.
authors.forename: Fanhui
authors.initials: F
authors.lastname: Meng
authors.affiliation: Department of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address: Doctor_yzy@139.com.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Yu
mesh_terms: D017209:Apoptosis; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics*
chemical_list: D007093:Imidazoles; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011804:Quinolines; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; C531198:dactolisib
keywords: Cervical cancer; Cervical carcinoma; NVP-BEZ235; PI3K/mTOR