PMID- 20102778 OWN - NLM STAT- MEDLINE DCOM- 20100330 LR - 20220330 IS - 1095-6859 (Electronic) IS - 0090-8258 (Linking) VI - 117 IP - 1 DP - 2010 Apr TI - Activation of mTOR signaling pathway contributes to survival of cervical cancer cells. PG - 103-8 LID - 10.1016/j.ygyno.2009.12.020 [doi] AB - OBJECTIVES: The mammalian target of rapamycin (mTOR) pathway is activated in a range of malignant cancers, but its role in human cervical cancer has not been well defined. This study aims to investigate the activation of mTOR pathway in cervical carcinomas and whether inhibition of mTOR with rapamycin, as well as specific siRNA, could lead to decreased proliferation, induced cell cycle arrest and apoptosis. METHODS: A cervical cancer tissue microarray was tested for activation of the mTOR pathway. The effects on HeLa cell survival and downstream signaling were determined following mTOR inhibition by increasing doses of rapamycin, or silencing by siRNA. RESULTS: The mTOR pathway is activated in cervical carcinomas. mTOR-specific siRNA effectively suppressed HeLa cell growth through mechanisms including inhibition of the cell cycle and increased apoptosis, which were similar to the mechanisms of rapamycin action. CONCLUSION: The mTOR signaling pathway is activated in cervical carcinomas. Inhibition of mTOR represents a potential therapeutic strategy for cervical cancers. CI - Copyright 2009 Elsevier Inc. All rights reserved. FAU - Ji, Jing AU - Ji J AD - Department of Reproductive Medicine, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, China. FAU - Zheng, Peng-Sheng AU - Zheng PS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100127 PL - United States TA - Gynecol Oncol JT - Gynecologic oncology JID - 0365304 RN - 0 (Antineoplastic Agents) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (RNA, Small Interfering) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - Q20Q21Q62J (Cisplatin) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Antineoplastic Agents/pharmacology MH - Apoptosis/drug effects/physiology MH - Cell Cycle/drug effects/physiology MH - Cell Survival/drug effects/physiology MH - Cisplatin/pharmacology MH - Down-Regulation MH - Female MH - HeLa Cells MH - Humans MH - Immunohistochemistry MH - Intracellular Signaling Peptides and Proteins/antagonists & inhibitors/*metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Protein Serine-Threonine Kinases/antagonists & inhibitors/biosynthesis/*metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - RNA, Small Interfering/genetics MH - Signal Transduction/drug effects MH - Sirolimus/pharmacology MH - TOR Serine-Threonine Kinases MH - Uterine Cervical Neoplasms/drug therapy/*metabolism/pathology EDAT- 2010/01/28 06:00 MHDA- 2010/03/31 06:00 CRDT- 2010/01/28 06:00 PHST- 2009/10/06 00:00 [received] PHST- 2009/12/15 00:00 [accepted] PHST- 2010/01/28 06:00 [entrez] PHST- 2010/01/28 06:00 [pubmed] PHST- 2010/03/31 06:00 [medline] AID - S0090-8258(09)01021-X [pii] AID - 10.1016/j.ygyno.2009.12.020 [doi] PST - ppublish SO - Gynecol Oncol. 2010 Apr;117(1):103-8. doi: 10.1016/j.ygyno.2009.12.020. Epub 2010 Jan 27.