Growth differentiation factor-11 inhibits the progression of acute myeloid leukemia and increases chemosensitivity by inhibiting cathepsin S

Growth differentiation factor-11 (GDF11) is an important member of the transforming growth factor-β superfamily and plays an important role in tumor progression. However, its role and prognostic value in acute myeloid leukemia (AML) have not been reported. We overexpressed GDF11 to investigate the effect of GDF11 on the behavior of AML cells. The effect of GDF11 on chemotherapy sensitivity was investigated in HL60 cells treated with 10 μM daunorubicin (DNR). Cell viability was detected using the cell counting kit-8 assay. Western blot was performed to analyze the expression levels of target proteins. GDF11 was associated with poor overall survival of AML patients. The proliferation of HL60 cells was inhibited by the transfection of pcDNA3.1-GDF11. GDF11 overexpression upregulated the expression of caspase3-p17 and Bax, while downregulating the Bcl-2 level. Importantly, the decreased cell proliferation and induced apoptosis by DNR were enhanced by GDF11 overexpression. Cathepsin S (CTSS) expression was inhibited by GDF11 in HL60 cells. The overexpression of CTSS attenuated the enhancement of GDF11 on chemotherapy sensitivity. In addition, CTSS activated the extracellular signal-regulated kinase 1 and 2 signaling pathway and inhibited endoplasmic reticulum stress in AML cells. In conclusion, GDF11 inhibited the growth and increased chemosensitivity through inhibiting CTSS expression in AML cells, providing potential therapeutic targets for AML treatment.