[LY294002 Enhaces Chemosensitivity of K562 Cells to Daunorubicin]

Abstract

Objective: To investigate the proliferation inhibition and pro-apoptosis effect of LY294002 (PI3K/AKT inhibtor) combined with daunorubicin (DNR) on the chronic myeloid leurenia cell line K562 and its possible mechanisms.

Methods: The effect of LY294002 and DNR on the proliferation of K562 cells in different treating time and concentration were measured by MTT assay. The cell cycle was determined by flow cytometry, the mRNA and protein expression of SKP2 , P27, BCL-2 and BAX were determined by RT-PCR and Western blot.

Results: LY294002 and DNR were able to inhibit the growth of K562 cells and promote apoptosis in time- and concentration-dependent manner (P＜0.05), both the cell proliferation-inhibiting rate and apoptosis rate in combination therapy group were higher than that in DNR-monotherapy group (P＜0.05). After K562 cells treated by LY294002 combined DNR for 36 h, the cells were statistically significantly reduced in G₂/M phase (P＜0.05), as compared with control group and DNR group. Compared with DNR group, the cell level of G₀/G₁ phase rased (P＜0.05) and cell level of S phase decreased (P＞0.05). Compared with DNR group, the expresson of SKP2 and BCL-2 mRNA decreased, and the expression of P27 mRNA increased in the combination therapy group (P＜0.05). The expression of BAX mRNA was not significantly different between different groups. The same result was found in the protein expression.

Conclusion: LY294002 has the sensibilizative effect on DNR chemotherapy, which may be relative with blocking the cell cycle and inducing cell apoptosis.