Published online Oct 15, 2023. doi: 10.4251/wjgo.v15.i10.1739
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
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.
To investigate the role and mechanism of action of deltonin in promoting gastric carcinoma (GC) cell apoptosis and chemosensitivity to cisplatin.
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.
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.
Deltonin can boost the chemosensitivity of GC cells to cisplatin via inactivating p38-MAPK and PI3K/AKT/mTOR signaling.
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.