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

  
@article{TCR16564,
	author = {Wei-Jian Sun and Bin He and Beng Yang and Wen-Di Hu and Jian Wu and Shu-Sen Zheng},
	title = {Autophagy blockade enhances the anti-cancer effect of Romidepsin in gastric cancer},
	journal = {Translational Cancer Research},
	volume = {6},
	number = {6},
	year = {2017},
	keywords = {},
	abstract = {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.},
	issn = {2219-6803},	url = {http://tcr.amegroups.com/article/view/16564}
}