Article Abstract

Autophagy blockade enhances the anti-cancer effect of Romidepsin in gastric cancer

Authors: Wei-Jian Sun, Bin He, Beng Yang, Wen-Di Hu, Jian Wu, Shu-Sen Zheng


Background: Autophagy, also known as macroautophagy, is a catabolic process that occurs in response to stress conditions to maintain cellular homeostasis. Inhibiting autophagy has been proposed as a new therapeutic strategy that could enhance the anticancer activity of histone deacetylase inhibitors. We previously demonstrated that romidepsin, a Food and Drug Administration-approved histone deacetylase inhibitor, acts as a potential anticancer agent. Therefore, this study aimed to develop effective combination treatment strategies to maximize the antitumor effects of romidepsin.
Methods: Regulation of autophagy by romidepsin was assessed by western blot assay, transmission electron microscopy (TEM), flow cytometric analysis and immunocytochemistry. The autophagy-inducing effect of a combination of romidepsin and hydroxychloroquine (HCQ) in gastric cancer (GC) was assessed in vitro and in vivo.
Results: Romidepsin induced autophagy in GC cells, possibly by regulating the extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR) signaling pathways. Furthermore, HCQ synergistically augmented the activity of romidepsin in vitro and in vivo.
Conclusions: Our results suggest that combining romidepsin and HCQ may represent a novel therapeutic strategy for GC.