Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Aug 15, 2023; 15(8): 1400-1411
Published online Aug 15, 2023. doi: 10.4251/wjgo.v15.i8.1400
Physcion increases the sensitivity of hepatocellular carcinoma to sorafenib through miRNA-370/PIM1 axis-regulated glycolysis
Xiao-Ping Pan, Bu-Ren Jiya, Feng Wang, Zhu Lan
Xiao-Ping Pan, Bu-Ren Jiya, Feng Wang, Department of Interventional Radiology, Inner Mongolia International Mongolian Hospital, Hohhot 016000, Inner Mongolia Autonomous Region, China
Zhu Lan, Graduate School, Inner Mongolia Medical University, Hohhot 016000, Inner Mongolia Autonomous Region, China
Author contributions: Pan XP and Wang F contributed to writing original draft; Jiya BR and Lan Z contributed to writing, review and editing, and methodology; all authors read and approved the final version of this paper.
Supported by National Natural Science Foundation of China, No. 81960782.
Institutional review board statement: The study was reviewed and approved by the Inner Mongolia International Mongolian Hospital Institutional Review Board, No. M459817.
Institutional animal care and use committee statement: The study was reviewed and approved by the Inner Mongolia International Mongolian Medical Hospital Institutional Review Board, No. M459817AE.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: All authors have no conflict of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Ping Pan, MD, Doctor, Department of Interventional Radiology, Inner Mongolia International Mongolian Hospital, No. 83 University East Street, Hohhot 016000, Inner Mongolia Autonomous Region, China. xiongmi7122504@163.com
Received: April 26, 2023
Peer-review started: April 26, 2023
First decision: June 15, 2023
Revised: June 16, 2023
Accepted: July 17, 2023
Article in press: July 17, 2023
Published online: August 15, 2023
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.

Keywords: Hepatocellular carcinoma, Sorafenib resistance, Physcion, Glycolysis, PIM1

Core tip: This study investigated the effects of physcion on sorafenib resistance of hepatocellular carcinoma (HCC) cells. Through utilizing in vitro and in vivo models, we found that physcion significantly enhanced the antitumor effects of sorafenib on sorafenib-resistant HCC cells, inducing apoptosis and suppressing cell growth. Further exploration on the mechanisms identified that physcion repressed HCC cells glycolysis by targeting the miRNA-370/PIM1 axis, which consequently sensitized HCC cells to sorafenib.