Knockdown of Beclin 1 inhibits vitamin K3‑induced autophagy, but promotes apoptosis of human hepatoma SMMC-7721 cells
Affiliations: Third Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, P.R. China, Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, P.R. China
- Published online on: July 26, 2010 https://doi.org/10.3892/mmr.2010.347
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The aim of the present study was to investigate the effects of Beclin 1 knockdown on spontaneous and vitamin K3 (VK3)-regulated autophagy, survival and apoptosis in human hepatocarcinoma SMMC-7721 cells, and to explore the potential mechanisms underlying the action of Beclin 1 knockdown in the processes of autophagy and apoptosis. A recombinant plasmid-expressing small interfering RNA (siRNA) targeting Beclin 1 mRNA was constructed and introduced into SMMC-7721 cells. The expression of Beclin 1 was determined by reverse transcription-polymerase chain reaction and Western blotting. Subsequently, the impact of Beclin 1 knockdown on spontaneous and VK3-induced autophagy, survival and apoptosis was determined. The expression of cyclin D1, cyclin-dependent kinase 4 (CDK4), Bcl-2, Bcl-xL and the activation of caspase-3 were examined by Western blotting. Transfection with the plasmid for Beclin 1 siRNA expression dramatically down-regulated Beclin 1 expression in SMMC-7721 cells. The knockdown of Beclin 1 expression significantly inhibited spontaneous and VK3-induced autophagy, but did not affect spontaneous proliferation and apoptosis in SMMC-7721 cells in vitro. By contrast, the silencing of Beclin 1 expression significantly enhanced the inhibition of survival and proliferation by VK3, and promoted VK3-induced apoptosis by significantly down-regulating cyclin D1, CDK4, Bcl-2 and Bcl-xL expression and enhancing caspase-3 activation in SMMC-7721 cells in vitro. Our data indicate that Beclin 1 is a positive regulator of autophagy, but a negative regulator of VK3-induced apoptosis in human hepatoma cells.