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
ARTICLE HIGHLIGHTS
Research background

Hepatocellular carcinoma (HCC) is one of the most malignant cancer types with high morbidity and mortality. Currently, patients with advanced HCC usually receive systemic local treatment with ablation or external irradiation along with sorafenib. Resistance to sorafenib has become a challenge in clinical treatment of HCC.

Research motivation

Physcion is a common bioactive anthraquinone that is a potential anticancer agent that has been reported to regulate multiple intracellular signaling pathways via targeting protein kinases, cell cycle, transcriptional factors, miRNAs, and apoptosis-related proteins. The excessive glycolysis of cancer cells compared with normal cells, named as Warburg effect, is a major characteristic of cancer and play a critical role in cancer initiation and development.

Research objectives

This work aimed to study the effect of physcion on glycolysis metabolism and sensitizing the HCC cells to sorafenib.

Research 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 assay.

Research 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 under 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.

Research conclusions

Physcion enhanced the sensitivity of HCC cells to sorafenib via enhancing miR-370 to suppress PIM1-promoted glycolysis.

Research perspectives

As a potential anticancer agent, physcion possibly enhances sensitivity in other therapy resistance. Based on the multiple cellular processes that are regulated by physcion, it is possible that PIM1-regulated glycolysis may not be the only mechanism underlying sorafenib sensitivity. Further studies such as high-throughput sequencing analysis may be conducted to explore the comprehensive and in-depth effects of physcion in cancer.