Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Sep 15, 2024; 16(9): 3980-3993
Published online Sep 15, 2024. doi: 10.4251/wjgo.v16.i9.3980
Resveratrol inhibits pancreatic cancer proliferation and metastasis by depleting senescent tumor-associated fibroblasts
He Jiang, Guo-Tai Wang, Zheng Wang, Qing-Yong Ma, Zhen-Hua Ma
He Jiang, Guo-Tai Wang, Zheng Wang, Qing-Yong Ma, Zhen-Hua Ma, Department of Hepatobiliary Surgery, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
Guo-Tai Wang, Department of Hepatobiliary Surgery, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang 712000, Shaanxi Province, China
Co-corresponding authors: Qing-Yong Ma and Zhen-Hua Ma.
Author contributions: Jiang H and Ma QY was conceived and designed the research; Jiang H and Wang GT performed the experiments; Wang Z and Ma ZH analysed the data; Jiang H wrote the manuscript. All authors thoroughly reviewed and approved the manuscript. It is important to note that all data presented in the manuscript were generated internally, and no external sources were used. Ma QY and Ma ZH have made equally significant contributions to the execution of the project. Their dedication, expertise, and hard work have been instrumental in ensuring the success of this project. They have both brought unique perspectives and skills to the table, complementing each other's strengths and working seamlessly as a team. Their commitment to excellence and their ability to collaborate effectively have set a high standard for the rest of the team to follow. It is clear that without their combined efforts, the project would not have achieved such results.
Supported by National Natural Science Foundation of China, No. 82072699; and Shaanxi Critical Research and Development Plan, No. 2021-SF363.
Institutional review board statement: The study was approved by the Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University (No. G-179).
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 Xi'an Jiaotong University.
Conflict-of-interest statement: All authors have no conflicts of interest.
Data sharing statement: It is important to note that all data presented in the manuscript were generated internally, and no external sources were used. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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: Zhen-Hua Ma, PhD, Professor, Department of Hepatobiliary Surgery, The First Affiliated Hospital, Xi’an Jiaotong University, No. 76 Yanta West Road, Xi’an 710061, Shaanxi Province, China. mzh@mail.xjtu.edu.cn
Received: March 27, 2024
Revised: June 26, 2024
Accepted: August 2, 2024
Published online: September 15, 2024
Processing time: 166 Days and 5.5 Hours
Abstract
BACKGROUND

Pancreatic cancer, a formidable gastrointestinal neoplasm, is characterized by its insidious onset, rapid progression, and resistance to treatment, which often lead to a grim prognosis. While the complex pathogenesis of pancreatic cancer is well recognized, recent attention has focused on the oncogenic roles of senescent tumor-associated fibroblasts. However, their precise role in pancreatic cancer remains unknown. Resveratrol is a natural polyphenol known for its multifaceted biological actions, including antioxidative and neuroprotective properties, as well as its potential to inhibit tumor proliferation and migration. Our current investigation builds on prior research and reveals the remarkable ability of resveratrol to inhibit pancreatic cancer proliferation and metastasis.

AIM

To explore the potential of resveratrol in inhibiting pancreatic cancer by targeting senescent tumor-associated fibroblasts.

METHODS

Immunofluorescence staining of pancreatic cancer tissues revealed prominent coexpression of α-SMA and p16. HP-1 expression was determined using immunohistochemistry. Cells were treated with the senescence-inducing factors known as 3CKs. Long-term growth assays confirmed that 3CKs significantly decreased the CAF growth rate. Western blotting was conducted to assess the expression levels of p16 and p21. Immunofluorescence was performed to assess LaminB1 expression. Quantitative real-time polymerase chain reaction was used to measure the levels of several senescence-associated secretory phenotype factors, including IL-4, IL-6, IL-8, IL-13, MMP-2, MMP-9, CXCL1, and CXCL12. A scratch assay was used to assess the migratory capacity of the cells, whereas Transwell assays were used to evaluate their invasive potential.

RESULTS

Specifically, we identified the presence of senescent tumor-associated fibroblasts within pancreatic cancer tissues, linking their abundance to cancer progression. Intriguingly, Resveratrol effectively eradicated these fibroblasts and hindered their senescence, which consequently impeded pancreatic cancer progression.

CONCLUSION

This groundbreaking discovery reinforces Resveratrol's stature as a potential antitumor agent and positions senescent tumor-associated fibroblasts as pivotal contenders in future therapeutic strategies against pancreatic cancer.

Keywords: Resveratrol; Pancreatic Cancer; Proliferation; Metastasis; Senescent; Fibroblasts

Core Tip: This study focused on the effect of resveratrol on pancreatic cancer-associated fibroblasts and confirmed the presence of senescent fibroblasts in pancreatic cancer. Resveratrol has a notable ability to curb pancreatic cancer proliferation and thus has potential as a promising antitumor agent. Therefore, this study identifies a new therapeutic target in pancreatic cancer treatment.