Silencing GnT‑V reduces oxaliplatin chemosensitivity in human colorectal cancer cells through N‑glycan alteration of organic cation transporter member 2

Cong,Xi; Liu,Xingwan; Dong,Xiaopeng; Fang,Shuoshuo; Sun,Zheng; Fan,Jianhui

doi:10.3892/etm.2020.9560

Silencing GnT‑V reduces oxaliplatin chemosensitivity in human colorectal cancer cells through N‑glycan alteration of organic cation transporter member 2

Authors:
- Xi Cong
- Xingwan Liu
- Xiaopeng Dong
- Shuoshuo Fang
- Zheng Sun
- Jianhui Fan
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Affiliations: Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China, Institute of Integrative Medicine, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
Published online on: December 7, 2020 https://doi.org/10.3892/etm.2020.9560
Article Number: 128
Copyright: © Cong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Organic cation transporter member 2 (OCT2) is an N‑glycosylated transporter that has been shown to be closely associated with the transport of antitumor drugs. Oxaliplatin, a platinum‑based drug, is used for the chemotherapy of colorectal cancer (CRC). However, oxaliplatin resistance is a major challenge in the treatment of advanced CRC. The aim of the present study was to better understand the mechanism underlying the chemosensitivity of CRC cells to oxaliplatin. The present study describes a potential novel strategy for enhancing oxaliplatin sensitivity involving the glycosylation of this drug transporter, specifically the modification of β‑1,6‑N‑acetylglucosamine (GlcNAc) residues by N‑acetylglucosaminyltransferase V (GnT‑V). The results revealed that the downregulation of GnT‑V inhibited the oxaliplatin chemosensitivity of CW‑2 cells. Furthermore, the knockdown of GnT‑V caused a marked reduction in the presence of β‑1,6‑GlcNAc structures on OCT2 and decreased the localization of OCT2 in the cytomembrane, which were associated with a reduced uptake of oxaliplatin in wild‑type and oxaliplatin‑resistant CW‑2 cells. Overall, the study provides novel insights into the molecular mechanism by which GnT‑V regulates the chemosensitivity to oxaliplatin, which involves the modulation of the drug transporter OCT2 by N‑glycosylation in CRC cells.

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