Activation of mTOR signaling pathway contributes to survival of cervical cancer cells.
OBJECTIVE
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.


CONCLUSIONS
The mTOR signaling pathway is activated in cervical carcinomas. Inhibition of mTOR represents a potential therapeutic strategy for cervical cancers.
Ji
Jing
J
Department of Reproductive Medicine, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, China.
Zheng
Peng-Sheng
PS
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology; D015536:Down-Regulation; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
D000970:Antineoplastic Agents; D002945:Cisplatin; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human