Bcl-2 down-regulation by small interfering RNA induces Beclin1-dependent autophagy in human SGC-7901 cells.

While Bcl-2 protein is involved in the regulation of apoptosis, recent research showed that Beclin1, described as the essential autophagy effector and haploinsufficient tumor suppressor, was originally isolated as a Bcl-2 interacting protein. Beclin1 interacts with Bcl-2 through a BH3 domain; nevertheless, the function of the anti-apoptotic gene, Bcl-2, in autophagy is not well understood. We explored the role of Bcl-2 in autophagy in human SGC-7901 cells in which Bcl-2 is overexpressed. Knockdown of Bcl-2 by small interfering RNA in human SGC-7901 cells downregulated Bcl-2 protein levels ∼82% and induced autophagy. Beclin1 protein, the first identified autophagy gene product, was induced by as much as 58%. Transmission electron microscopy and DNA fragmentation assay showed that autophagy was enhanced, but not apoptosis, in Bcl-2 siRNA treated cells. The results provide evidence that knockout the anti-apoptotic gene Bcl-2 induces autophagy in SGC-7901 cells and Bcl-2 specific siRNA may be used as a potential therapeutic strategy in gastric cancer cells that overexpress Bcl-2.