Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Oct 15, 2023; 15(10): 1739-1755
Published online Oct 15, 2023. doi: 10.4251/wjgo.v15.i10.1739
Deltonin enhances gastric carcinoma cell apoptosis and chemosensitivity to cisplatin via inhibiting PI3K/AKT/mTOR and MAPK signaling
Lin Yang, Ya-Nan Liu, Yi Gu, Qi Guo
Lin Yang, Intensive Care Unit, Second Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
Ya-Nan Liu, Department of Obstetrics and Gynecology, Second Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
Yi Gu, Nursing Department of Obstetrics and Gynecology, Second Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
Qi Guo, Department of Radiotherapy, Second Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
Author contributions: Yang L and Liu YN contributed equally to this work and are co-first authors. Yang L and Liu YN conceived and designed the experiments; Yang L, Liu YN, Gu Y, and Guo Q performed the experiments; Yang L, Liu YN, Gu Y, and Guo Q contributed to the statistical analysis; Yang L, Liu YN, and Guo Q wrote the paper; and all authors read and approved the final manuscript.
Institutional review board statement: Our study was approved by the Ethics Review Committee of the Second Affiliated Hospital of Soochow University (approval No.: SZSH-2020-042).
Institutional animal care and use committee statement: The animal experiments were approved by the Ethics Review Committee of the Second Affiliated Hospital of Soochow University (approval No. SZSH-2020-042).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data sets used and 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: Qi Guo, Doctor, Doctor, Department of Radiotherapy, Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Road, Suzhou 215006, Jiangsu Province, China. guoqi456258@163.com
Received: April 6, 2023
Peer-review started: April 6, 2023
First decision: April 19, 2023
Revised: May 23, 2023
Accepted: July 19, 2023
Article in press: July 19, 2023
Published online: October 15, 2023
ARTICLE HIGHLIGHTS
Research background

Despite being the main clinical treatment modality for advanced gastric cancer (GC), chemoradiotherapy is still difficult to achieve the expected effect due to the early diagnosis of GC and the characteristics of distant metastasis and drug resistance. Deltonin, an active ingredient in traditional Chinese medicine, shows anti-cancer effects on many malignancies.

Research motivation

This study attempted to optimize the treatment strategies for advanced GC and enhance the therapeutic effect on patients from a pharmacological mechanism perspective.

Research objectives

Here, we investigated the role and mechanism of action of deltonin in promoting GC cell apoptosis and chemosensitivity to cisplatin.

Research methods

In this study, gastric cancer cell lines (AGS, HGC-27, and MKN-45 cells) were treated with deltonin. Then, apoptosis was observed, and the expression of apoptosis-related proteins (Bax, Bid, Bad, and Fas), DNA repair-related proteins (Rad51 and MDM2), and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin (PI3K/AKT/mTOR-MAPK) proteins was detected by Western blot analysis. In addition to this, the effect of deltonin on the chemosensitivity of GC cells to cisplatin was evaluated by in vivo and in vitro experiments

Research results

Treating GC cells (AGS, HGC-27, and MKN-45) with deltonin resulted in reduced proliferation ability and increased apoptosis rate; of these, HGC-27 cells exhibited the best proliferation capability and the lowest apoptosis rate. Our experiments demonstrated the ability of deltonin to promote GC cell apoptosis and chemosensitivity to cisplatin by lowering PI3K/AKT/mTOR and p38-MAPK-associated protein levels, offering novel insights into the mechanism of drug action.

Research conclusions

Deltonin enhances the chemosensitivity of GC cells to cisplatin by inhibiting the p38-MAPK and PI3K/AKT/mTOR signaling pathways.

Research perspectives

This study has verified that deltonin is able to regulate GC cell apoptosis as well as chemosensitivity to cisplatin through the PI3K/AKT/mTOR and p38-AMPK signaling pathways by in vivo and in vitro experiments. Such results provide a new direction for drug therapy of gastric cancer. However, the study of the regulatory role of the pathways in this study was limited and could not fully elucidate its mechanism of action. Therefore, further analysis as well as nude mouse experiments and more cellular experiments are needed to excavate the mechanism.