Elevated phosphatidylinositol 3-kinase activation and its clinicopathological significance in cervical cancer.
OBJECTIVE
The objective was to study the role of PI3K signaling in the development of cervical cancer and the antitumor effect of PI3K inhibitors.


METHODS
PI3K protein and mRNA expression of cervical cancer and non-neoplastic tissues were analyzed by Western blotting and RT-PCR. PI3K/Akt/mTOR pathway components in HeLa cells were assessed by immunocytochemistry and Western blotting. The inhibitive effect of LY294002 on HeLa cells was studied using MTT assay and flow cytometry.


RESULTS
PI3K protein expression was detected in 25 out of 31 tumor specimens. Compared with non-neoplastic tissues, significant overexpression was observed in tumor tissues. For PI3K overexpression with all clinicopathological features, a decreasing trend in adenocarcinoma, advanced stage, and grade was observed. PI3K inhibitor LY294002 efficiently inhibited HeLa cell growth with IC50 of 20.77 microM, and induced apoptosis. The apoptotic rate was 36% at 3h after LY294002 treatment. These pharmacological roles of LY294002 might be played through the PI3K/Akt/mTOR signaling pathway.


CONCLUSIONS
The PI3K signaling pathway was implicated in the development of cervical cancer. The activation of its signaling molecules might have clinical implications. Novel targeted therapies for the PI3K/Akt/mTOR signaling pathway components could provide a useful adjuvant therapeutic strategy for cervical cancer.
Zhang
Xiao-Yan
XY
The Obstetrics and Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011, PR China.
Zhang
Hai-Yan
HY
Zhang
Peng-Nan
PN
Lu
Xin
X
Sun
Hong
H
D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology
D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D058570:TOR Serine-Threonine Kinases; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C546842:MTOR protein, human