抑制xCT可改善由CD44变体9表达诱导的胃癌对5-氟尿嘧啶的耐药性。

Inhibiting xCT Improves 5-Fluorouracil Resistance of Gastric Cancer Induced by CD44 Variant 9 Expression.

作者信息

Miyoshi Sawako, Tsugawa Hitoshi, Matsuzaki Juntaro, Hirata Kenro, Mori Hideki, Saya Hideyuki, Kanai Takanori, Suzuki Hidekazu

机构信息

Division of Gastroenterology and Hepatology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.

Department of Biochemistry, Keio University School of Medicine, Tokyo, Japan.

出版信息

Anticancer Res. 2018 Nov;38(11):6163-6170. doi: 10.21873/anticanres.12969.

DOI:10.21873/anticanres.12969

PMID:30396933

Abstract

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.

摘要

背景/目的：癌症干细胞（CSCs）在化疗耐药中起关键作用。CD44是CSCs的细胞表面标志物。CD44变体9（CD44v9）与胱氨酸-谷氨酸反向转运体（xCT）相互作用，是胃癌的不良预测因子。我们研究了CD44v9表达对5-氟尿嘧啶（5-FU）耐药性的影响，以及xCT抑制剂柳氮磺胺吡啶（SASP）改善耐药性的疗效。