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

Abstract

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 <i>in vitro</i> 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.