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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Inhibiting xCT Improves 5-Fluorouracil Resistance of Gastric Cancer Induced by CD44 Variant 9 Expression
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Inhibiting xCT Improves 5-Fluorouracil Resistance of Gastric Cancer Induced by CD44 Variant 9 Expression

机译:抑制XCT提高了CD44变体9表达诱导的胃癌的5-氟尿嘧啶抗性

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Background/Aim: Cancer stem cells (CSCs) play a critical role in resistance to chemotherapy. CD44 is a cell surface marker of CSCs. CD44 variant 9 (CD44v9) interacts with a cystine-glutamate antiporter (xCT) and is an unfavorable predictive factor in gastric cancer. We investigated the impact of CD44v9 expression on 5-fluorouracil (5-FU) resistance and the efficacy of the xCT inhibitor, sulfasalazine (SASP), in improving drug resistance. Materials and Methods: The human gastric cancer cell line MKN28 was transfected with pRc/CMV plasmids encoding human CD44 or CD44v9, which were used for in vitro and in vivo experiments. Results: CD44v9 expression results in 5-FU resistance by increasing intracellular glutathione and suppressing the drug-induced production of reactive oxygen species (ROS). SASP improved the drug sensitivity of CD44v9-expressing cells. Conclusion: Inhibition of xCT improved the clinical efficacy of chemotherapy against gastric cancer. CD44v9 expression can be a novel biomarker to predict resistance against 5-FU in gastric cancer.
机译:背景/目的:癌症干细胞(CSCs)在抗化疗中发挥着关键作用。 CD44是CSCs的细胞表面标志物。 CD44变体9(CD44V9)与胱氨酸 - 谷氨酸抗原物(XCT)相互作用,是胃癌中不利的预测因素。我们调查了CD44V9表达对5-氟尿嘧啶(5-FU)抗性和XCT抑制剂,磺苯胺嗪(SASP),提高耐药性的影响。材料和方法:用编码人CD44或CD44V9的PRC / CMV质粒转染人胃癌细胞系MKN28,其用于体外和体内实验。结果:CD44V9表达通过增加细胞内谷胱甘肽和抑制药物诱导的反应性氧(ROS)产生5-FU抗性。 SaSP改善了表达CD44V9表达细胞的吸毒敏感性。结论:XCT的抑制改善了化疗对胃癌的临床疗效。 CD44V9表达可以是一种新的生物标志物,以预测胃癌中5-FU的抗性。

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