Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Nov 15, 2024; 16(11): 4468-4476
Published online Nov 15, 2024. doi: 10.4251/wjgo.v16.i11.4468
Effects of invigorating-spleen and anticancer prescription on extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway in colon cancer mice model
Wei Wang, Jing Wang, Xiu-Xiu Ren, Hai-Long Yue, Zheng Li
Wei Wang, Zheng Li, Department of Integrated Traditional Chinese and Western Medicine Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, Liaoning Province, China
Jing Wang, Xiu-Xiu Ren, Hai-Long Yue, The First Clinical School, Liaoning University of Chinese Medicine, Shenyang 110847, Liaoning Province, China
Co-first authors: Wei Wang and Jing Wang.
Author contributions: Li Z conceived the work, supervised the writing, and provided intellectual input; Wang W and Wang J were responsible for most of the manuscript; All authors conducted the literature search.
Supported by Liaoning Provincial Science and Technology Department Project, No. 2023JH2/101700149; and Open Fund Project of Liaoning University of Traditional Chinese Medicine, No. zyzx2205.
Institutional animal care and use committee statement: All animal husbandry and experiments were conducted in strict accordance with the regulations for the care and use of laboratory animals, approved by the Institutional Animal Care and Use Committee of the Liaoning University of Chinese Medicine, No. 2021012125.
Conflict-of-interest statement: All authors state that they have no conflicts of interest to report.
Data sharing statement: All authors agree data sharing, and available from the Corresponding author by request at oabqddc@163.com.
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: Zheng Li, MD, Chief Physician, Department of Integrated Traditional Chinese and Western Medicine Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang 110042, Liaoning Province, China. fox_dl1984@163.com
Received: August 6, 2024
Revised: September 6, 2024
Accepted: September 29, 2024
Published online: November 15, 2024
Processing time: 80 Days and 1.9 Hours
Abstract
BACKGROUND

Colon cancer (CC) is one of the most common malignant tumors in the gastrointestinal system. Overall, CC had the third highest incidence but the second highest mortality rate globally in 2020. Nowadays, CC is mainly treated with capecitabine chemotherapy regimen, supplemented by radiotherapy, immunotherapy and targeted therapy, but there are still limitations, so Chinese medicine plays an important role.

AIM

To investigate the effects of invigorating-spleen and anticancer prescription (ISAP) on body weight, tumor inhibition rate and expression levels of proteins in extracellular-signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) signaling pathway in CC mice model.

METHODS

The CC mice model were established and the mice were randomly divided into 5 groups, including the control group, capecitabine group, the low-dose, medium-dose and high-dose groups of ISAP, with 8 mice in each group, respectively. After 2 weeks of intervention, the body weight and tumor inhibition rate of mice were observed, and the expression of RAS, ERK, phosphorylated ERK (p-ERK), C-MYC and matrix metalloproteinase 2 (MMP2) proteins in the tissues of tumors were detected.

RESULTS

Compared with the control group, the differences of body weight before and after treatment was much smaller in the groups of ISAP, with the smallest difference in the high-dose group of ISAP, while the capecitabine group had the greatest difference, indicating ISAP had a significant inhibiting effect on the growth of transplanted tumor in mice. The expression of RAS protein was decreased in the low- and medium-dose groups of ISAP, and the change of p-ERK was significant in the medium- and high- dose groups of ISAP. MMP2 protein expression was significantly decreased in both the low-dose and medium-dose groups of ISAP. There were no significant changes in ERK in the ISAP group compared to the capecitabine group, while RAS, MMP2, and C-MYC protein expression were reduced in the ISAP group. The expression level of C-MYC protein decreased after treated with ISAP, and the decrease was the most significant in the medium-dose group of ISAP.

CONCLUSION

ISAP has a potential inhibiting effect on transplanted tumor in mice, and could maintain the general conditions, physical strength and body weight of mice. The expression levels of RAS, p-ERK, MMP2 and c-myc were also decreased to a certain extent. By inhibiting the expression of upstream proteins, the expression levels of downstream proteins in ERK/MAPK signaling pathway were significantly decreased. Therefore, it can be concluded that ISAP may exert an anti-tumor effect by blocking the ERK/MAPK signaling pathway and inhibiting the expression of MMP2 and c-myc proteins.

Keywords: Colon cancer; Invigorating-spleen and anticancer formula; Extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway; Mice model; C-MYC

Core Tip: The incidence and mortality of intestinal cancer is increasing year by year. Due to the limited therapeutic means and low survival rate of advanced patients, and the easy development of drug resistance to chemotherapy, targeting and immunotherapy, we have found that spleen-healthy anticancer formula can play an anti-tumor role through the extracellular-signal-regulated kinase/mitogen-activated protein kinase signaling pathway and inhibit the expression of matrix metalloproteinase 2 and c-myc.