The inhibitory effect of quercetin on chemotherapeutic drug resistance of gastric cancer through forkhead box D3 signaling pathway

Abstract

Most gastric cancer patients have cancer cell metastasis at the time of being diagnosed. Cisplatin chemotherapy can slow down the development of gastric cancer, but the drug resistance will develop after a long time of chemotherapy. Previous studies have found that quercetin improves resistance of chemotherapy drugs. Therefore, this study intends to explore quercetin’s role in gastric cancer. SGC-7901 drug-resistant cell line was cultured and intervened. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay assessed cell proliferation, cell survival rate, IC50 value and sensitivity along with analysis of cell apoptosis, proliferation by colony formation assay and qRT-PCR (real-time reverse transcription-PCR) and Western blot detection of FOXD3 (Forkhead box D3) levels. Gastric cancer xenograft tumor mouse model was established to assess its in vivo role. The drug-resistant cell model of gastric cancer was successfully constructed and quercetin inhibited cell survival to a certain extent and improved its chemosensitivity. The pro-apoptotic effect of quercetin on cisplatin chemotherapy resistance in gastric cancer is related to the increased FOXD3 level. Quercetin can directly regulate the expression of FOXD3, which is an activation effect. The inhibition rate of gastric cancer mice in vivo was the most prominent in the quercetin+drug resistance group. The tumor-bearing site was significantly reduced and the number of surviving mice was the highest, whose tumor volume was consistently lower than that of other groups. Conclusively, quercetin has a strong anti-tumor effect. It can inhibit gastric cancer cell activity and accelerate apoptosis by activating FOXD3 signaling pathway.