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

被引：46
作者：
Miyoshi, Sawako [1 ]
Tsugawa, Hitoshi [2 ]
Matsuzaki, Juntaro [1 ]
Hirata, Kenro [1 ]
Mori, Hideki [1 ]
Saya, Hideyuki [3 ]
Kanai, Takanori [1 ]
Suzuki, Hidekazu [4 ,5 ]
机构：
[1] Keio Univ, Dept Med, Div Gastroenterol & Hepatol, Sch Med, Tokyo, Japan
[2] Keio Univ, Dept Biochem, Sch Med, Tokyo, Japan
[3] Keio Univ, Inst Adv Med Res, Div Gene Regulat, Sch Med, Tokyo, Japan
[4] Keio Univ, Fellowship Training Ctr, Sch Med, Tokyo, Japan
[5] Keio Univ, Med Educ Ctr, Sch Med, Tokyo, Japan
来源：
ANTICANCER RESEARCH | 2018年 / 38卷 / 11期
关键词：
Gastric cancer; cancer stem cells; CD44; variant; 9; 5-fluorouracil; xCT inhibitor; sulfasalazine; HELICOBACTER-PYLORI CAGA; PANCREATIC-CANCER; STEM-CELLS; IDENTIFICATION; SULFASALAZINE; GROWTH; DRUG; METASTASIS; CARCINOMA;
D O I：
10.21873/anticanres.12969
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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.
引用
收藏
页码：6163 / 6170
页数：8
相关论文
共 38 条
  • [1] Gastric Cancer, Version 3.2016
    Ajani, Jaffer A.
    D'Amico, Thomas A.
    Almhanna, Khaldoun
    Bentrem, David J.
    Chao, Joseph
    Das, Prajnan
    Denlinger, Crystal S.
    Fanta, Paul
    Farjah, Farhood
    Fuchs, Charles S.
    Gerdes, Hans
    Gibson, Michael
    Glasgow, Robert E.
    Hayman, James A.
    Hochwald, Steven
    Hofstetter, Wayne L.
    Ilson, David H.
    Jaroszewski, Dawn
    Johung, Kimberly L.
    Keswani, Rajesh N.
    Kleinberg, Lawrence R.
    Korn, W. Michael
    Leong, Stephen
    Linn, Catherine
    Lockhart, A. Craig
    Ly, Quan P.
    Mulcahy, Mary F.
    Orringer, Mark B.
    Perry, Kyle A.
    Poultsides, George A.
    Scott, Walter J.
    Strong, Vivian E.
    Washington, Mary Kay
    Weksler, Benny
    Willett, Christopher G.
    Wright, Cameron D.
    Zelman, Debra
    McMillian, Nicole
    Sundar, Hema
    [J]. JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK, 2016, 14 (10): : 1286 - 1312
  • [2] Prospective identification of tumorigenic breast cancer cells (vol 100, pg 3983, 2003)
    Al-Hajj, M
    Wicha, MS
    Benito-Hernandez, A
    Morrison, SJ
    Clarke, MF
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (11) : 6890 - 6890
  • [3] Induction of CD44 Variant 9-Expressing Cancer Stem Cells Might Attenuate the Efficacy of Chemoradioselection and Worsens the Prognosis of Patients with Advanced Head and Neck Cancer
    Aso, Takeichiro
    Matsuo, Mioko
    Kiyohara, Hideyuki
    Taguchi, Kenichi
    Rikimaru, Fumihide
    Shimokawa, Mototsugu
    Segawa, Yuichi
    Higaki, Yuichiro
    Umeno, Hirohito
    Nakashima, Tadashi
    Masuda, Muneyuki
    [J]. PLOS ONE, 2015, 10 (03):
  • [4] Changing Trends in Stomach Cancer Throughout the World
    Balakrishnan M.
    George R.
    Sharma A.
    Graham D.Y.
    [J]. Current Gastroenterology Reports, 2017, 19 (8)
  • [5] Targeting stromal remodeling and cancer stem cell plasticity overcomes chemoresistance in triple negative breast cancer
    Cazet, Aurelie S.
    Hui, Mun N.
    Elsworth, Benjamin L.
    Wu, Sunny Z.
    Roden, Daniel
    Chan, Chia-Ling
    Skhinas, Joanna N.
    Collot, Raphael
    Yang, Jessica
    Harvey, Kate
    Johan, M. Zahied
    Cooper, Caroline
    Nair, Radhika
    Herrmann, David
    McFarland, Andrea
    Deng, Niantao
    Ruiz-Borrego, Manuel
    Rojo, Federico
    Trigo, Jose M.
    Bezares, Susana
    Caballero, Rosalia
    Lim, Elgene
    Timpson, Paul
    O'Toole, Sandra
    Watkins, D. Neil
    Cox, Thomas R.
    Samuel, Michael S.
    Martin, Miguel
    Swarbrick, Alexander
    [J]. NATURE COMMUNICATIONS, 2018, 9
  • [6] Disruption of xCT inhibits cancer cell metastasis via the caveolin-1/β-catenin pathway
    Chen, R-S
    Song, Y-M
    Zhou, Z-Y
    Tong, T.
    Li, Y.
    Fu, M.
    Guo, X-L
    Dong, L-J
    He, X.
    Qiao, H-X
    Zhan, Q-M
    Li, W.
    [J]. ONCOGENE, 2009, 28 (04) : 599 - 609
  • [7] Molecular Origins of Cancer Molecular Basis of Metastasis
    Chiang, Anne C.
    Massague, Joan
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2008, 359 (26) : 2814 - 2823
  • [8] Prospective identification of tumorigenic prostate cancer stem cells
    Collins, AT
    Berry, PA
    Hyde, C
    Stower, MJ
    Maitland, NJ
    [J]. CANCER RESEARCH, 2005, 65 (23) : 10946 - 10951
  • [9] Phenotypic characterization of human colorectal cancer stem cells
    Dalerba, Piero
    Dylla, Scott J.
    Park, In-Kyung
    Liu, Rui
    Wang, Xinhao
    Cho, Robert W.
    Hoey, Timothy
    Gurney, Austin
    Huang, Emina H.
    Simeone, Diane M.
    Shelton, Andrew A.
    Parmiani, Giorgio
    Castelli, Chiara
    Clarke, Michael F.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (24) : 10158 - 10163
  • [10] Therapeutic Implications of the Cancer Stem Cell Hypothesis
    Diehn, Maximilian
    Cho, Robert W.
    Clarke, Michael F.
    [J]. SEMINARS IN RADIATION ONCOLOGY, 2009, 19 (02) : 78 - 86
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