[Reversal effect of PI-3K/Akt pathway inhibitor LY294002 on multidrug resistance of ovarian cancer cell line A2780/Taxol]

Xiao-Yan Shi, Xiao-Jun Cai, Jian-Xiang Lei, Feng-Jun Cao, Dong-Feng Pan, Ping Chen
Ai Zheng, Aizheng, Chinese Journal of Cancer 2008, 27 (4): 343-7

BACKGROUND & 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.

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