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

  • World J Gastrointest Oncol. 2023 Oct 15;15(10):1739-1755. doi: 10.4251/wjgo.v15.i10.1739.
Lin Yang  1 ,  Ya-Nan Liu  2 ,  Yi Gu  3 ,  Qi Guo  4
Affiliations
  • 1. Intensive Care Unit, Second Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.
  • 2. Department of Obstetrics and Gynecology, Second Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.
  • 3. Nursing Department of Obstetrics and Gynecology, Second Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.
  • 4. Department of Radiotherapy, Second Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China. [email protected].
PMID: 37969408 DOI: 10.4251/wjgo.v15.i10.1739
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
Apoptosis; Axis; Chemotherapy; Cisplatin; Deltonin; Gastric carcinoma.
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