Abstract:
Objective: To explore the effect of PI 3K/AKT inhibitor LY294002 on sensitization to chemotherapy (cisplatin and paclitaxel) on human ovarian cancer cell lines A 2780 and SKOV 3. Methods:Chemosensitivity of A 2780 and SKOV 3 cells to chemotherapy was measured using MTT assay when LY 294002 was applied with cisplatin or paclitaxel individually or in combination. The apoptotic rates were detected by flow cytometry. The expression of AKT and p-AKT proteins was an-alyzed using Western blot. Results: Inhibition of A2780and SKOV 3 cell proliferation was increased significantly by cisplatin and paclitaxel in combination with LY294002 (P<0.05). LY 294002 had synergistic effects with cisplatin and paclitaxel (com -bination index< 1). The apoptotic index was increased by the joint application of the three drugs. Phosphorylated AKT pro-tein levels in A 2780and SKOV 3 cells were clearly inhibited by LY 294002, compared to the control group. There was a statistical significance in the differences between the two groups (P<0.01). Conclusion:LY294002 can effectively enhance the sensitivity of A2780and SKOV 3 cells to cisplatin and paclitaxel. Inhibition of the PI3K/AKT signaling pathway can increase the chemotherapeutic effect of cisplatin and paclitaxel on human ovarian cancer cells.