Abstract
Resistance to apoptosis induced by chemotherapy is still an obstacle for the treatment of chronic myeloid leukemia (CML). Numerous studies have indicated that upregulation of hepatocyte growth factor (HGF) protein expression reduced apoptosis induced by various factors. However, whether HGF has any effect on apoptosis induced by VP-16 (etoposide) in CML cells and its underlying mechanisms are unclear. HGF was overexpressed in the K562 cell line using transfection. The protein and mRNA expression levels, and the concentration of HGF were measured using western blot analysis, reverse transcription-quantitative (RT-qPCR) and ELISA respectively. Apoptosis in the K562 cell line was determined using flow cytometry and western blot analysis. Changes in cell viability were measured using a MTT assay. RT-qPCR and western blot analysis revealed that HGF was successfully upregulated at both the mRNA and protein expression levels in the K562 cell line, respectively. After VP-16 treatment, the number of apoptotic cells overexpressing HGF was lower compared with that in cells transfected with the empty vector. Mechanistic investigation revealed that overexpression of HGF led to the increase in Bcl-2 protein expression level and inhibition of caspase-3/9 activation. Furthermore, HGF overexpression resulted in activation of the PI3K/Akt signaling pathway. Therefore, the results of the present study revealed that targeting HGF could be used as a strategy to overcome VP-16 resistance in CML.