Deltonin enhances gastric carcinoma cell apoptosis and chemosensitivity to cisplatin via inhibiting PI3K/AKT/mTOR and MAPK signaling

作     者：Lin Yang Ya-Nan Liu Yi Gu Qi Guo 

作者机构：Intensive Care UnitSecond Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina Department of Obstetrics and GynecologySecond Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina Nursing Department of Obstetrics and GynecologySecond Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina Department of RadiotherapySecond Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina 

出 版 物：《World Journal of Gastrointestinal Oncology》 (世界胃肠肿瘤学杂志(英文版)(电子版))

年 卷 期：2023年第15卷第10期

页      面：1739-1755页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：Deltonin Gastric carcinoma Cisplatin Apoptosis Chemotherapy Axis 

摘      要：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-diphenyltet-razolium 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.