[Reversal effect of PI-3K/Akt pathway inhibitor LY294002 on multidrug resistance of ovarian cancer cell line A2780/Taxol].
OBJECTIVE
Previous studies had showed that phosphatidylinositol 3 kinase (PI-3K) can suppress cell apoptosis. The inhibitor of PI-3K has been used to investigate the mechanisms of PI-3K-induced oncogenesis. This study was to investigate the reversal effect of LY294002, a PI-3K/Akt inhibitor, on paclitaxel-resistance of ovarian carcinoma cell line A2780/Taxol.


METHODS
A2780/Taxol cells were treated with LY294002. Cell apoptosis was analyzed by flow cytometry (FCM). The 50% inhibition concentration (IC50) of paclitaxel for A2780/Taxol cells was determined by MTT assay. The expression of multidrug resistance 1 (MDR1) mRNA was assessed by reverse transcription-polymerase chain reaction (RT-PCR). The expression of phosphated Akt and P-glycoprotein (P-gp) were detected by Western blot.


RESULTS
When treated for 24 h, the apoptosis rate of A2780/Taxol cells was significantly higher in 10 and 50 micromol/L LY294002 groups than in control group [(8.84+/-1.65)% and (20.78+/-2.47)% vs. (1.25+/-0.78)%, P<0.05], the IC50 of paclitaxel for A2780/Taxol cells was decreased significantly (P<0.01) with the highest reverse efficiency of (78.08+/-0.37)%. Moreover, the expression of MDR1 gene, and the phosphorylation of Akt and P-gp in A2780/Taxol cells were decreased.


CONCLUSIONS
The activation of PI-3K/Akt pathway plays an important role in paclitaxel-resistance of ovarian carcinoma cells. PI-3K/Akt inhibitor, LY294002 has a reversal effect on the paclitaxel-resistance of A2780/Taxol cells.
Shi
Xiao-Yan
XY
Department of Oncology, People's Hospital, Yunyang Medical College, Shiyan, Hubei, 442000, PR China. sxy_70@sina.com
Cai
Xiao-Jun
XJ
Lei
Jian-Xiang
JX
Cao
Feng-Jun
FJ
Pan
Dong-Feng
DF
Chen
Ping
P
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D009025:Morpholines / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects*
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt