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
Processing time: 186 Days and 22.9 Hours
Abstract
BACKGROUND

As an active ingredient derived from Dioscorea zingiberensis C.H. Wright, deltonin has been reported to show anti-cancer effects in a variety of malignancies.

AIM

To investigate the role and mechanism of action of deltonin in promoting gastric carcinoma (GC) cell apoptosis and chemosensitivity to cisplatin.

METHODS

The GC cell lines AGS, HGC-27, and MKN-45 were treated with deltonin and then subjected to flow cytometry and 3-(4,5-dimethylthiazol-2-yl)-3,5-diphenyltetrazolium bromide assays for cell apoptosis and viability determination. Western blot analysis was conducted to examine alterations in the expression of apoptosis-related proteins (Bax, Bid, Bad, and Fas), DNA repair-associated proteins (Rad51 and MDM2), and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin (PI3K/AKT/mTOR) and p38-mitogen-activated protein kinase (MAPK) axis proteins. Additionally, the influence of deltonin on GC cell chemosensitivity to cisplatin was evaluated both in vitro and in vivo.

RESULTS

Deltonin treatment weakened viability, enhanced apoptosis, and dampened DNA repair in GC cell lines in a dose-dependent pattern. Furthermore, deltonin mitigated PI3K, AKT, mTOR, and p38-MAPK phosphorylation. HS-173, an inhibitor of PI3K, attenuated GC cell viability and abolished deltonin inhibition of GC cell viability and PI3K/AKT/mTOR and p38-MAPK pathway activation. Deltonin also promoted the chemosensitivity of GC cells to cisplatin via repressing GC cell proliferation and growth and accelerating apoptosis.

CONCLUSION

Deltonin can boost the chemosensitivity of GC cells to cisplatin via inactivating p38-MAPK and PI3K/AKT/mTOR signaling.

Keywords: Deltonin; Gastric carcinoma; Cisplatin; Apoptosis; Chemotherapy; Axis

Core Tip: Chemoradiotherapy is currently the mainstay of clinical treatment for advanced gastric carcinoma (GC). However, chemoradiotherapy is difficult to achieve the desired results due to the challenges of early diagnosis of GC and the characteristics of distant metastasis and drug resistance. This study attempted to enhance the efficacy of GC clinical treatment from a pharmacological mechanism perspective.