Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jun 15, 2024; 16(6): 2742-2756
Published online Jun 15, 2024. doi: 10.4251/wjgo.v16.i6.2742
Aspirin suppresses hepatocellular carcinoma progression by inhibiting platelet activity
Li-Jun Zhao, Zhi-Yin Wang, Wei-Ting Liu, Li-Li Yu, Hao-Nan Qi, Jie Ren, Chen-Guang Zhang
Li-Jun Zhao, Zhi-Yin Wang, Hematology Laboratory, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, Henan Province, China
Li-Jun Zhao, Wei-Ting Liu, Li-Li Yu, Hao-Nan Qi, Jie Ren, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Medical Technology, Xinxiang Medical University, Xinxiang 453003, Henan Province, China
Chen-Guang Zhang, School of Public Health, Xinxiang Medical University, Xinxiang 453003, Henan Province, China
Co-first authors: Li-Jun Zhao and Zhi-Yin Wang.
Author contributions: Zhao LJ and Wang ZY contributed equally to this work; Zhao LJ, Wang ZY, and Zhang CG designed the research study; Zhao LJ, Wang ZY, Liu WT, Yu LL, Qi HN, and Ren J performed the research; Zhao LJ, Wang ZY, and Zhang CG analyzed the data and wrote the manuscript; and all authors have read and approved the final manuscript. Zhao LJ and Wang ZY contributed equally to this work as co-first authors due to the fact that they contributed efforts of equal substance throughout the research process, such as designing and performing experiments, analyzing data, writing manuscripts and addressing queries. Indeed, we believe that designating Zhao LJ and Wang ZY as co-first authors are fitting for our manuscript as it accurately reflects our team’s collaborative spirit, equal contributions, and diversity.
Institutional review board statement: The study was reviewed and approved by the Institutional review board Committee of the Xinxiang Medical University (approval number: XYLL-2020537).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Xinxiang Medical University (approval number: XYLL-2020537).
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: All the data used to support the findings of this study are included within the article.
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: Chen-Guang Zhang, PhD, Professor, School of Public Health, Xinxiang Medical University, No. 601 Jinsui Road, Xinxiang, 453003, Henan Province, China. 051085@xxmu.edu.cn
Received: January 10, 2024
Revised: March 20, 2024
Accepted: April 16, 2024
Published online: June 15, 2024
Processing time: 156 Days and 13 Hours
Abstract
BACKGROUND

Hepatocellular carcinoma (HCC) is the most common malignant liver disease in the world. Platelets (PLTs) are known to play a key role in the maintenance of liver homeostasis and the pathophysiological processes of a variety of liver diseases. Aspirin is the most classic antiplatelet agent. However, the molecular mechanism of platelet action and whether aspirin can affect HCC progression by inhibiting platelet activity need further study.

AIM

To explore the impact of the antiplatelet effect of aspirin on the development of HCC.

METHODS

Platelet-rich plasma, platelet plasma, pure platelet, and platelet lysate were prepared, and a coculture model of PLTs and HCC cells was established. CCK-8 analysis, apoptosis analysis, Transwell analysis, and real-time polymerase chain reaction (RT-PCR) were used to analyze the effects of PLTs on the growth, metastasis, and inflammatory microenvironment of HCC. RT-PCR and Western blot were used to detect the effects of platelet activation on tumor-related signaling pathways. Aspirin was used to block the activation and aggregation of PLTs both in vitro and in vivo, and the effect of PLTs on the progression of HCC was detected.

RESULTS

PLTs significantly promoted the growth, invasion, epithelial-mesenchymal transition, and formation of an inflammatory microenvironment in HCC cells. Activated PLTs promoted HCC progression by activating the mitogen-activated protein kinase/protein kinase B/signal transducer and activator of transcription three (MAPK/ AKT/STAT3) signaling axis. Additionally, aspirin inhibited HCC progression in vitro and in vivo by inhibiting platelet activation.

CONCLUSION

PLTs play an important role in the pathogenesis of HCC, and aspirin can affect HCC progression by inhibiting platelet activity. These results suggest that antiplatelet therapy has promising application prospects in the treatment and combined treatment of HCC.

Keywords: Platelets, Antiplatelet therapy, Hepatocellular carcinoma, Aspirin, Antitumor

Core Tip: Previous studies have revealed the role of platelet plasma and its derivatives in tumorigenesis and development. Aspirin has also been shown to reduce the risk of hepatocellular carcinoma (HCC). However, the molecular mechanism of platelet action and whether aspirin can affect the progression of HCC by inhibiting platelet activity need to be further studied. Therefore, our study focused on exploring the functional mechanisms of platelets in the progression of HCC and using aspirin as an example to evaluate the application prospects of antiplatelet therapy. These findings will provide a potential strategy for the treatment of HCC and combination therapy.