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Abstract

BET Bromodomain Inhibitors OTX015 Promote Killing of Hepatocellular Carcinoma Cells through Pharmacological Effect and By Inhibiting the Expression of Programmed Death Ligand-1

Author(s): Wei Zhang*, Yuanxi Gao, Jinxing Ji, Gang Zhou, Maohua Chen, Yan Cai, Hushuang Yang, Ziliang Chen and Huiqin Zhang
Department of Oncology, Traditional Chinese Medicine Hospital of China Three Gorges University, Yichang Hospital of Traditional Chinese Medicine, 1Department of Oncology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei Province 443000, China

Correspondence Address:
Wei Zhang, Department of Oncology, Traditional Chinese Medicine Hospital of China Three Gorges University, Yichang Hospital of Traditional Chinese Medicine, Yichang, Hubei Province 443000, China, E-mail: a13377664449@126.com


Bromodomain and extra-terminal domain inhibitors target bromodomain-containing proteins and are currently being evaluated as anti-cancer agents. In this study, we found that bromodomain and extraterminal domain inhibitor OTX015 can effectively inhibit the proliferation of hepatocellular carcinoma cells and promote the apoptosis of hepatocellular carcinoma cells. At the same time, the anticancer effect of OTX015 is better than that of JQ1, a similar bromodomain and extra-terminal domain inhibitor. In addition, we also found that OTX015, like JQ1 can inhibit the expression of programmed death-ligand 1 in hepatocellular carcinoma cells induced by interferon alpha. We also demonstrated that this inhibition was achieved by inhibiting the binding of bromodomain and extra-terminal domain protein to the promoter of programmed death-ligand 1 and inhibiting the transcriptional activity of programmed death-ligand 1. When treated hepatocellular carcinoma cells with bromodomain and extra-terminal domain inhibitor, peripheral blood mononuclear cells can kill hepatocellular carcinoma cells. Finally, we also detected the expression levels of bromodomain and extra-terminal domain protein, bromodomain-containing protein 2, bromodomain-containing protein 4 and programmed death-ligand 1 in patient samples. The results showed that the expression levels of bromodomain-containing protein 2 and bromodomain-containing protein 4 were correlated with that of programmed death-ligand 1 in some patients. Therefore, bromodomain and extraterminal domain protein inhibitor OTX015 may be a small molecule drug with dual anti-tumor effects.

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