DNA damage regulated autophagy modulator 1 recovers the function of apoptosis-stimulating of p53 protein 2 on inducing apoptotic cell death in Huh7.5 cells

摘要

Overexpression of apoptosis-stimulating of p53 protein 2 (ASPP2) can induce apoptotic cell death in hepatoma cells, which contributes to a killing effect of ASPP2 on treating hepatocellular carcinoma (HCC). In the present study, ASPP2 overexpression failed to induce apoptotic cell death in the HCC Huh7.5 cell line, but promoted autophagy development by inhibiting AKT/mTOR pathway. Inhibition of autophagy using 3-methyladenosine recovered the function of ASPP2 on inducing apoptotic cell death, indicating that ASPP2-induced autophagy has an anti-apoptotic role in Huh7.5 cells. A previous study demonstrated that ASPP2-induced autophagy could induce apoptosis in a CHOP-and DRAM-dependent manner, in which CHOP is involved in the initiation of autophagy and DRAM allows autophagy to induce apoptosis. In the present study, CHOP and DRAM were not involved in ASPP2-induced autophagy; however, the induction of DRAM overexpression recovered the apoptosis-inducing function of ASPP2, indicating that DRAM overexpression switches the role of ASPP2-induced autophagy from anti-apoptotic to pro-apoptotic in Huh7.5 cells. Thus, in combination with DRAM, ASPP2 may better perform its pro-apoptotic role by preventing the occurrence of anti-apoptotic autophagy.