[Effects of DOT1L Inhibitor EPZ-5676 Combined with Chemotherapeutic Drugs on Prolifiration and Apoptosis of RS 4;11 Cells].

OBJECTIVE: To investigate the synergistic antiproliferative and inducing-apoptotic effect of EPZ-5676 combined with chemotherapeutic drugs on acute lymploblastic leukemia(ALL).

METHODS: The MLL rearragement positive (MLL-r+ ) ALL cell line RS4;11 was treated with EPZ-5676 alone and its combination with 5 kinds of chemotherapeutic drugs of ALL, the CCK-8 method was used to assay the inhibitory rate of leukemia cells treated with EPZ-5676 and chemotherapeutic drugs alone and their combination; the compusyn software was used to evaluate the relationthip between inhibitory rate (Fa) of combined drugs for leukemia cells and combination index (CI), and to determine the interaction of drugs; the flow cytometry with Annexin V-FITC/PI double staining was used to detect the apoptotic rate of RS4;11 treated EPZ-5676, GC, VCR, CTX, epirubicin and VP16 alone and combination of EPZ-5676 with them and to compare the inducing apoptotic effect of combined drugs.

RESULTS: The combination of EPZ-5672 with GC or VCR or VP16 showed synergistic antiproliferative effect; the combination of EPZ-5676 with TX or epirubicin displayed antogonistic effect. As compared with blank control group, 5, 10 and 25 µmol/L EPZ-5676 did not affected on apoptosis of RS4;11 cells, but 5 µmol/L EPZ-5676 combined with VCR of GC possessed synergistically inducing apoptotic effect (56.87% vs 12.93%)(P<0.01), (8.86% vs 5.28%)(P<0.05).

CONCLUSION: The EPZ-5676 combined with GC or VCR or VP16 possesses synergistic antiproliferative effect on RS4;11 cells, the effect of EPZ-5676 alone on apoptosis of RS4;11 cells is no significant, but the combination of low concentration EPZ-5676 with VCR or GC displays synergistically inducing apoptotic effect.