Physcion increases the sensitivity of hepatocellular carcinoma to sorafenib through miRNA-370/PIM1 axis-regulated glycolysis.

ABSTRACT

BACKGROUND: Resistance to sorafenib has become a challenge in clinical treatment of hepatocellular carcinoma (HCC). Physcion is a common bioactive anthraquinone that has potential as an anticancer agent. AIM: To study the effect of physcion on sensitizing HCC cells to sorafenib. METHODS: Sorafenib-resistant HCC cells were established and treated with sorafenib and/or physcion. The cell viability, proliferation and apoptosis were measured by cell counting kit-8, colony formation, flow cytometry, and in vivo xenograft model. Glucose uptake, lactate acid production, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR) were measured to analyze glycolysis. Expression of glycolysis-related regulators was assessed by western blotting. RESULTS: The addition of physcion significantly enhanced the antitumor effects of sorafenib on sorafenib-resistant HCC cells, manifested by enhanced apoptosis and suppressed cell growth. The glucose uptake, lactate acid production, and ECAR were elevated, and OCR was suppressed by physcion treatment. The level of PIM1 was elevated and miR-370 was suppressed in sorafenib-resistant HCC cells compared with the parental cells, which was suppressed by physcion treatment. Inhibition of miR-370 notably reversed the effects of physcion on sorafenib-resistant HCC cells. CONCLUSION: Our data indicated that physcion enhanced the sensitivity of HCC cells to sorafenib by enhancing miR-370 to suppress PIM1-promoted glycolysis.