Inhibiting xCT improves 5-fluorouracil resistance of gastric cancer induced by CD44 variant 9 expression

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6163-6170
Number of pages8
JournalAnticancer Research
Volume38
Issue number11
DOIs
Publication statusPublished - 2018 Nov 1

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Keywords

  • 5-fluorouracil
  • Cancer stem cells
  • CD44
  • CD44 variant 9
  • Gastric cancer
  • Sulfasalazine
  • xCT inhibitor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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