The efficacy of sorafenib against hepatocellular carcinoma is enhanced by 5‐aza‐mediated inhibition of ID1 promoter methylation

Abstract

Sorafenib resistance greatly restricts its clinical application in patients with hepatocellular carcinoma (HCC). Numerous studies have reported that ID1 exerts a crucial effect in cancer initiation and development. Our previous research revealed an inhibitory role of ID1 in sorafenib resistance. However, the upstream regulatory mechanism of ID1 expression is unclear. Here, we discovered that ID1 expression is negatively correlated with promoter methylation, which is regulated by DNMT3B. Knockdown of DNMT3B significantly inhibited ID1 methylation status and resulted in an increase of ID1 expression. The demethylating agent 5‐aza‐2′‐deoxycytidine (5‐aza) remarkably upregulated ID1 expression. The combination of 5‐aza with sorafenib showed a synergistic effect on the inhibition of cell viability.

Keywords

• DNA methylation
• drug resistance
• hepatocellular carcinoma
• ID1
• sorafenib