Department of Biochemistry, Wannan Medical College, Wuhu, Anhui, P.R.China.
Anhui Province Key Laboratory of Active Biological Macromolecules, Wuhu, Anhui, P.R.China.
Asian Pac J Cancer Prev. 2020 May 1;21(5):1269-1274. doi: 10.31557/APJCP.2020.21.5.1269.
One of the most common treatment for gastric cancer is chemotherapy, however, multiple drug resistance (MDR) induce the therapeutic effect which result in the failure of anticancer therapy. Dihydromyricetin (DMY) was reported to have antitumor activities on various human cancer cells in vitro, our previous studies demonstrated that DMY combined with mitomycin has inhibitory effect on proliferation of gastric carcinoma cells. However, the underlying role of DMY reversing the MDR of gastric carcinoma is poor understood. The aim of this study was to evaluate the reversal effect of DMY on MDR and investigate the molecular mechanisms in vitro.
Using MTT assay, we identified the toxicity of DMY on SGC7901 and SGC7901/5-FU cells. The effect of DMY on 5-FU induced apoptosis was evaluated by flow cytometry analysis. Using RT-PCR and Western blot, we determined the MDR1 mRNA and protein expression.
DMY induced growth inhibition in both SGC7901 and SGC7901/5-FU cells, the IC50 value was 13.64±1.15 µg/mL, 20.69±1.82 µg/mL respectively. DMY treatment sensitized SGC7901/5-FU cells to cytotoxicity of 5-FU. The combination of DMY with 5-FU increased the apoptosis rate (9.91%, 16.67%) comparing with 5-FU alone (5.25%). Comparing with the control group, the MDR1 mRNA and protein expression in SGC7901/5-FU cells after treatment of DMY decreased significantly (P< 0.05).
In brief, our study demonstrated that DMY effectively reversed multi-drug resistance occurring in SGC7901/5-FU cells cultured in vitro, and the potential mechanism was involved in the downregulation of the MDR1 expression.
胃癌的最常见治疗方法之一是化疗，然而，多药耐药（MDR）导致治疗效果不佳，导致抗癌治疗失败。二氢杨梅素（DMY）已被报道在体外对各种人类癌细胞具有抗肿瘤活性，我们之前的研究表明，DMY 与丝裂霉素联合使用对胃癌细胞的增殖具有抑制作用。然而，DMY 逆转胃癌多药耐药的潜在作用尚不清楚。本研究旨在评估 DMY 在体外逆转 MDR 的作用，并探讨其分子机制。
通过 MTT 法测定 DMY 对 SGC7901 和 SGC7901/5-FU 细胞的毒性。通过流式细胞术分析评估 DMY 对 5-FU 诱导的细胞凋亡的影响。采用 RT-PCR 和 Western blot 法测定 MDR1mRNA 和蛋白表达。
DMY 诱导 SGC7901 和 SGC7901/5-FU 细胞生长抑制，IC50 值分别为 13.64±1.15µg/mL 和 20.69±1.82µg/mL。DMY 处理使 SGC7901/5-FU 细胞对 5-FU 的细胞毒性更加敏感。与单独使用 5-FU 相比，DMY 与 5-FU 联合使用可增加细胞凋亡率（9.91%，16.67%）。与对照组相比，DMY 处理后 SGC7901/5-FU 细胞中 MDR1mRNA 和蛋白表达明显降低（P<0.05）。
总之，本研究表明 DMY 能有效逆转体外培养的 SGC7901/5-FU 细胞多药耐药，其潜在机制可能涉及下调 MDR1 表达。
