Inhibition of autophagy in hepatocarcinoma cells promotes chemotherapeutic agent-induced apoptosis during nutrient deprivation

Abstract

Autophagy is a lysosome-dependent process involved in protein and organelle degradation. It has been suggested that autophagy is activated in nutrient-deficient condition and plays an important role in protecting cells from nutrient shortage. However, the effect of autophagy on chemotherapy during nutrient deficiency has been rarely researched. In the present study, we discovered that hepatocarcinoma cells exhibit chemoinsensitivity accompanied by the activation of autophagy when cultured in nutrient-deprived medium. Inhibition of autophagy by 3-methyladenine or siRNA-targeted Beclin 1 increased the nutrient deprivation-induced apoptosis and chemosensitivity in hepatocarcinoma cells. Furthermore, decreased mitochondrial mass was detected when cells underwent autophagy. The present study suggests that induction of autophagy confers a survival advantage for hepatocarcinoma cells during nutrient deprivation, not only rescuing cells from nutrient deficiency-induced cell apoptosis, but also protecting cells from chemotherapy-induced cell death. Combined usage of the inhibition of autophagy and conventional chemotherapeutic agents could be an effective therapy for hepatocarcinoma during nutrient deprivation.