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
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.
This study attempted to optimize the treatment strategies for advanced GC and enhance the therapeutic effect on patients from a pharmacological mechanism perspective.
Here, we investigated the role and mechanism of action of deltonin in promoting GC cell apoptosis and chemosensitivity to cisplatin.
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
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.
Deltonin enhances the chemosensitivity of GC cells to cisplatin by inhibiting the p38-MAPK and PI3K/AKT/mTOR signaling pathways.
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.