Beclin-1 knockdown decreases proliferation, invasion and migration of Ewing sarcoma SK-ES-1 cells via inhibition of MMP-9

摘要

Although Beclin-1, a well-known key regulator of autophagy, has been demonstrated to serve a function in a number of disorders, including cancer, aging and degenerative diseases, its biological function in Ewing sarcoma (ES) remains unresolved. The objective of the present study was to determine the in vitro effect of Beclin-1 knockdown on the growth and malignant phenotype of ES SK-ES-1 cells, which have increased endogenous expression of Beclin-1 compared with RD-ES cells, and to investigate the underlying molecular mechanism. Cell proliferation, invasion and migration were investigated using CCK-8, Boyden chamber Transwell, and wound healing assays, respectively. Western blot analysis was used to detect expression levels of matrix metalloproteinase (MMP) -2 and MMP-9, which are associated with the malignant phenotype. Beclin-1 knockdown significantly inhibited proliferation, invasion and migration of SK-ES-1 cells. Western blot analysis revealed that Beclin-1 knockdown caused a significant reduction in the expression of MMP-9; no marked changes in MMP-2 expression were observed in the si-Beclin-1 group compared with the control group. The results of the present study suggest that Beclin-1 serves a function in proliferation, tumor progression and inhibition of autophagy in ES, and demonstrates it's potential as a target to increase the efficacy of anticancer agents.