TY - JOUR T1 - Inhibiting xCT Improves 5-Fluorouracil Resistance of Gastric Cancer Induced by CD44 Variant 9 Expression JF - Anticancer Research JO - Anticancer Res SP - 6163 LP - 6170 DO - 10.21873/anticanres.12969 VL - 38 IS - 11 AU - SAWAKO MIYOSHI AU - HITOSHI TSUGAWA AU - JUNTARO MATSUZAKI AU - KENRO HIRATA AU - HIDEKI MORI AU - HIDEYUKI SAYA AU - TAKANORI KANAI AU - HIDEKAZU SUZUKI Y1 - 2018/11/01 UR - http://ar.iiarjournals.org/content/38/11/6163.abstract N2 - 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. ER -