Abstract:
Objective To study the effect of the phosphatidylinositol 3'-kinase (PI3K/Akt) inhibitor LY294002 during chemotherapy on the paclitaxel-resistant ovarian cancer cell line A2780/Taxol.
Methods The effect of treatment with LY294002 on A2780/Taxol cell lines was determined based on the 50% inhibition concentration (IC50) of paclitaxel, and on cell proliferation using the cholecystokinin octapeptide (CCK-8) assay. The apoptotic rates and cell cycle stages were detected by flow cytometry. The expression of PI3K/ Akt, its phosphorylated form p-Akt, and phosphorylated P-glycoprotein (P-gp) protein was analyzed using Western blot.
Results The CCK-8 results showed that the proliferation of A2780/Taxol cell lines after 24 h since being treated with LY294002 was significantly slower compared with the untreated A2780/Taxol cell lines. The IC50 of paclitaxel in A2780/Taxol cells treated with LY294002 was also significantly lower than that in the original A2780/Taxol cell line. Flow cytometry demonstrated that the apoptotic ratio of the experiment group was significantly higher than that of the control group. Both groups showed some changes in the cell cycle, and there were statistically significant differences between the two groups (P < 0.05). Phosphorylated Akt and P-gp protein levels in A2780/Taxol cells were inhibited by LY294002, compared with the untreated A2780/Taxol cells.
Conclusion The PI3K/Akt inhibitor LY294002 has a reversal effect on the paclitaxel-resistance of the A2780/Taxol cell line.