FAK gene silencing enhances chemotherapeutic drug sensitivity in leukemic cells

AIM: To investigate the effect of focal adhesion kinase(FAK) gene silencing on chemotherapeutic drug sensitivity in leukemic cells.METHODS: Lentiviral-FAK-shRNA was transfected into BCR/ABL-BaF3 leukemic cells.The protein expression of FAK was detected by Western blotting.BCR/ABL-BaF3 leukemic cells were treated with different concentrations of imatinib in vitro,and the apoptosis was determined by labeling with Annexin V.A murine model of leukemia was established and the mice were treated with FAK shRNA and imatinib.Survival time and distribution of leukemic cells in bone marrow and spleen of the mice were monitored.RESULTS: FAK shRNA was successfully constructed and effectively inhibited FAK gene expression.With 5 μmol/L imatinib treatment,the percentages of apoptotic cells in vector control group and FAK shRNA group were(9.76±1.97)% and(21.90±3.20)%,respectively,and significant difference between these 2 groups(P0.05) was observed.With 50 μmol/L imatinib treatment,the percentages of apoptotic cells in vector control group and FAK shRNA group were(56.10±6.00)% and(82.10±5.70)%,respectively,also with significant difference between these 2 groups(P0.05).Compared with vector control group,the mice in FAK gene silencing group displayed significantly prolonged survival time.Moreover,60 days after injection of leukemic cells,the percentages of leukemic cells in bone marrow and spleen of the mice were significantly decreased in FAK gene silencing group as compared with those in vector control group.CONCLUSION: FAK gene silencing promotes the efficacy of chemotherapeutic drug in leukemic cells,indicating that FAK gene silencing might be considered as a new therapeutic strategy for leukemia.