Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan.
Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
PLoS One. 2021 Dec 7;16(12):e0260533. doi: 10.1371/journal.pone.0260533. eCollection 2021.
Chemotherapy drugs have limited efficacy in breast cancer due to multidrug resistance generated by cancer cells against anticancer drugs. In this study, we developed a novel derivative, 2, 3, 5, 4'-tetrahydroxystilbene (TG1) by modifying 2, 3, 5, 4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG). In-vivo zebrafish embryo tests revealed that TG1 showed low toxicity. The equitoxic combination of DOX or DTX with TG1 in MCF-7/Adr reduced the IC50 of DOX or DTX, and the combination index (CI) showed strong synergistic effects in the 1:3 molar ratio of DTX: TG1 and 1:5 molar ratio of DOX: TG1. Moreover, fluorescence images confirmed the cellular uptake of DOX when combined with TG1 in MCF-7/Adr. Western blotting analysis indicated downregulation of p-glycoprotein (P-gp) after MCF-7/Adr treated with TG1. In conclusion, the combined therapy of DTX or DOX and TG1 increases drug efficacy via suppressing the p-glycoprotein efflux pump. These results suggest that TG1 may have potential use for breast cancer patients, especially those with multidrug resistance.
化疗药物在乳腺癌中的疗效有限，这是由于癌细胞对抗癌药物产生的多药耐药性。在这项研究中，我们通过修饰 2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷（THSG）开发了一种新型衍生物 2,3,5,4'-四羟基二苯乙烯（TG1）。体内斑马鱼胚胎试验表明 TG1 毒性较低。在 MCF-7/Adr 中，DOX 或 DTX 与 TG1 的等毒性联合用药降低了 DOX 或 DTX 的 IC50，并且在 DTX:TG1 的 1:3 摩尔比和 DOX:TG1 的 1:5 摩尔比下，CI 显示出强烈的协同作用。此外，荧光图像证实了 MCF-7/Adr 中 DOX 与 TG1 联合使用时的细胞摄取。Western blot 分析表明，TG1 处理 MCF-7/Adr 后，p-糖蛋白（P-gp）下调。总之，DTX 或 DOX 与 TG1 的联合治疗通过抑制 p-糖蛋白外排泵增加了药物疗效。这些结果表明，TG1 可能对乳腺癌患者，特别是多药耐药患者具有潜在的应用价值。
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