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Ubenimex Reverses MDR in Gastric Cancer Cells by Activating Caspase-3-Mediated Apoptosis and Suppressing the Expression of Membrane Transport Proteins
Joint Authors
Guo, Qie
Jing, Fan-jing
Qu, Hai-jun
Xu, Wen
Han, Bing
Xing, Xiao-min
Ji, Hong-yan
Jing, Fan-Bo
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-02-20
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
Gastric cancer (GC) is one of the most malignant tumors, accounting for 10% of deaths caused by all cancers.
Chemotherapy is often necessary for treatment of GC; the FOLFOX regimen is extensively applied.
However, multidrug resistance (MDR) of GC cells prevents wider application of this treatment.
Ubenimex, an inhibitor of CD13, is used as an immune adjuvant to treat hematological malignancies.
Here, we demonstrate that CD13 expression positively correlates with MDR development in GC cells.
Moreover, Ubenimex reverses the MDR of SGC7901/X and MKN45/X cells and enhances their sensitivity to FOLFOX, in part by decreasing CD13 expression, which is accompanied by downregulation of Bcl-xl, Bcl-2, and survivin expression; increased expression of Bax; and activation of the caspase-3-mediated apoptotic cascade.
In addition, Ubenimex downregulates expression of membrane transport proteins, such as P-gp and MRP1, by inhibiting phosphorylation in the PI3K/AKT/mTOR pathway to increase intracellular accumulations of 5-fluorouracil and oxaliplatin, a process for which downregulation of CD13 expression is essential.
Therefore, the present results reveal a previously uncharacterized function of CD13 in promoting MDR development in GC cells and suggest that Ubenimex is a candidate for reversing the MDR of GC cells.
American Psychological Association (APA)
Guo, Qie& Jing, Fan-jing& Qu, Hai-jun& Xu, Wen& Han, Bing& Xing, Xiao-min…[et al.]. 2019. Ubenimex Reverses MDR in Gastric Cancer Cells by Activating Caspase-3-Mediated Apoptosis and Suppressing the Expression of Membrane Transport Proteins. BioMed Research International،Vol. 2019, no. 2019, pp.1-14.
https://search.emarefa.net/detail/BIM-1125346
Modern Language Association (MLA)
Guo, Qie…[et al.]. Ubenimex Reverses MDR in Gastric Cancer Cells by Activating Caspase-3-Mediated Apoptosis and Suppressing the Expression of Membrane Transport Proteins. BioMed Research International No. 2019 (2019), pp.1-14.
https://search.emarefa.net/detail/BIM-1125346
American Medical Association (AMA)
Guo, Qie& Jing, Fan-jing& Qu, Hai-jun& Xu, Wen& Han, Bing& Xing, Xiao-min…[et al.]. Ubenimex Reverses MDR in Gastric Cancer Cells by Activating Caspase-3-Mediated Apoptosis and Suppressing the Expression of Membrane Transport Proteins. BioMed Research International. 2019. Vol. 2019, no. 2019, pp.1-14.
https://search.emarefa.net/detail/BIM-1125346
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1125346