Details

Autor(en) / Beteiligte

• Ren, Mengting
• Zhou, Xinxin
• Gu, Mengli
• Jiao, Wenrui
• Yu, Mosang
• Wang, Yamei
• Liu, Sha
• Yang, Jinpu
• Ji, Feng

Titel

Resveratrol synergizes with cisplatin in antineoplastic effects against AGS gastric cancer cells by inducing endoplasmic reticulum stress‑mediated apoptosis and G2/M phase arrest

Ist Teil von

• Oncology reports, 2020-10, Vol.44 (4), p.1605-1615

Ort / Verlag

Athens: Spandidos Publications

Erscheinungsjahr

2020

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• Gastric cancer (GC) is a common gastrointestinal malignancy, and cisplatin (DDP) is an important component of chemotherapeutic regimens for GC. However, the application of DDP is limited by its dose-dependent systemic toxicity. Resveratrol (RES) is a natural polyphenol compound that has chemopreventive and therapeutic effects against various cancers, including GC. However, whether RES can sensitize GC cells to DDP remains unknown. Following RES/DDP combination treatment, cell viability was determined by Cell Counting Kit-8 and colony-forming assays, and cell apoptosis and the cell cycle were detected by FITC-Annexin V/PI staining assay and PI staining assay, respectively, followed by flow cytometry. Moreover, western blotting was performed to evaluate the protein expression levels, and the intracellular free [Ca.sup.2+] concentration was determined by a Fluo-4 AM probe after cell cotreatment with RES and DDP. The present results demonstrated that RES/DDP combination treatment significantly inhibited cell viability, promoted cell apoptosis and induced G2/M phase arrest in AGS cells. In addition, it was determined that RES combined with DDP significantly increased the levels of Bax, cleaved poly-ADP-ribose polymerase (PARP), glucose-regulated protein 78 (GRP78), PRKR-like ER kinase (PERK), p-eukaryotic translation initiation factor 2a (p-eIF2a), CCAAT/enhancer binding protein homologous protein (CHOP) and cleaved caspase-12, whereas Bcl-2 expression was downregulated following RES/DDP cotreatment. Moreover, RES/DDP cotreatment significantly upregulated phosphorylated cyclin-dependent kinase 1 (p-CDKl, Tyrl5), [p21.sup.Wafl/Cipl] and [p27.sup.Kipl] protein levels and downregulated Cdc25C protein levels. In conclusion, RES and DDP synergistically inhibited the growth of the gastric adenocarcinoma cell line AGS by inducing endoplasmic reticulum stress-mediated apoptosis and G2/M phase arrest via activation of the PERK/eIF2a/activating transcription factor 4 (ATF4)/CHOP signaling pathway and caspase-12 and by inactivating the CDKl-cyclin Bl complex. These results indicated that RES is a promising adjuvant for DDP during GC chemotherapy.