Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2025; 17(3): 102187
Published online Mar 15, 2025. doi: 10.4251/wjgo.v17.i3.102187
To investigate the effect and mechanism of tetrahydrocurcumin on hepatocellular carcinoma based on phosphoinositide 3-kinases/AKT signaling pathway
Zhuo-Cong Bao, Zhao-Dong Liu, Ye Zhang, Hui-Jun Dai, Hui Jia, Fu Ren, Ning Li, Lu Zhao, Yi-Wei Wang, Shang-Yu Lv, Yan Zhang
Zhuo-Cong Bao, Zhao-Dong Liu, Ye Zhang, Graduate School, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
Hui-Jun Dai, Guangxi Medical University Cancer Hospital, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Hui Jia, School of Traditional Chinese Medicine, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
Fu Ren, Ning Li, Yi-Wei Wang, Yan Zhang, Key Laboratory of Human Ethnic Specificity and Phenomics of Critical Illness in Liaoning Province, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
Fu Ren, Ning Li, Yan Zhang, Key Laboratory of Phenomics in Shenyang, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
Ning Li, Lu Zhao, Yan Zhang, Department of Biochemistry, School of Basic Medicine, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
Yi-Wei Wang, Molecular Morphology Laboratory, College of Basic Medical Sciences, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
Shang-Yu Lv, Batch 2022, Clinical Medicine, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
Yan Zhang, International Education School, International Exchange and Cooperation Office, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
Co-first authors: Zhuo-Cong Bao and Zhao-Dong Liu.
Author contributions: Bao ZC, Zhang Y, and Liu ZD performed most of the bench work, analyzed the data and wrote the manuscript, Bao ZC and Liu ZD contributed equally as co-first authors; Dai HJ responsible for experimental guidance; Ren F performed technical consultant; Li N contributed new reagents and analytic tools; Lv SY collected relevant references and perfecting the manuscript; Zhang Y experimental design; Bao ZC, Liu ZD, Zhang Y, Dai HJ, Jia H, Ren F, Li N, Zhao L, Wang YW, Lv SY, and Zhang Y read and approved the final manuscript.
Supported by the Central Government Guidance Local Science and Technology Development Fund, No. 2023JH6/100100021; Liaoning Province Education Department Foundation of China, No. JYTMS20231393; Scientific Research Project of Liaoning Province Education Department, No. SYYX2019015; Science and Technology Fund of Shenyang Medical College, No. 20171004, Shenyang Medical College Master’s Science and Technology Innovation Fund, No. Y20220509; and Liaoning Provincial Department of Education Scientific Research Project, No. LJ212410164032.
Institutional review board statement: This study did not involve human or animal subjects, and thus, no institutional review board statement was required.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at zhangyan@symc.edu.cn. Participants gave informed consent for data sharing.
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: Yan Zhang, Associate Professor, PhD, International Education School, International Exchange and Cooperation Office, Shenyang Medical College, No. 146 North Huanghe Street, Shenyang 110034, Liaoning Province, China. zhangyan@symc.edu.cn
Received: October 11, 2024
Revised: November 20, 2024
Accepted: January 2, 2025
Published online: March 15, 2025
Processing time: 126 Days and 2.8 Hours
Abstract
BACKGROUND

Liver cancer has a high incidence and mortality worldwide, especially in China. Herein, we investigated the therapeutic effect and mechanism of tetrahydrocurcumin against hepatocellular carcinoma (HCC), with a focus on the of phosphoinositide 3-kinases (PI3K)/AKT signaling pathway.

AIM

To investigate the effects and mechanism of tetrahydrocurcumin in HCC cell lines HepG2 and Huh7.

METHODS

Using Metascape, we analyzed the potential targets of tetrahydrocurcumin in HCC. Molecular docking validation was performed using SYBYL2.0. Cell Counting Kit-8, wound healing, and transwell assays were performed to evaluate the effects of tetrahydrocurcumin on HepG2 and Huh7 cell migration, invasion, and apoptosis. The expression of PI3K/AKT signaling pathway-related proteins was detected by western blotting.

RESULTS

Network pharmacology and molecular docking showed that tetrahydrocurcumin has high binding affinity for phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha. In vitro experiments demonstrated that tetrahydrocurcumin suppressed the migration and invasion of liver cancer cells, promoted their apoptosis, and downregulated the expression of p-PI3K, p-AKT, and B cell leukemia/lymphoma 2, while upregulating caspase-3, p53, and B cell leukemia/lymphoma 2 associated X.

CONCLUSION

In summary, tetrahydrocurcumin suppresses PI3K/AKT signaling, promotes apoptosis, and prevents the migration and invasion of liver cancer cells.

Keywords: Hepatocellular carcinoma; Tetrahydrocurcumin; Network pharmacology; Molecular docking; PI3K/AKT signaling pathway

Core Tip: In this comprehensive study, we delved into the anti-cancer potential of tetrahydrocurcumin, meticulously assessing its impact on the proliferation, migration, and invasion of liver cancer cell lines HepG2 and Huh7. Our findings revealed that tetrahydrocurcumin not only effectively inhibited the proliferation and migration of hepatocellular carcinoma cells but also significantly induced apoptosis through the phosphoinositide 3-kinases/AKT signaling pathway, underscoring its therapeutic potential in combating liver cancer.