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Published in: Medical Oncology 2/2014

01-02-2014 | Original Paper

Txr1: an important factor in oxaliplatin resistance in gastric cancer

Authors: Jingtao Bi, Zhigang Bai, Xuemei Ma, Jianning Song, Yantong Guo, Jingming Zhao, Xin Yi, Shiwei Han, Zhongtao Zhang

Published in: Medical Oncology | Issue 2/2014

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Abstract

Oxaliplatin-based chemotherapy is the main treatment regimen for gastric cancer (GC), but can fail because of drug resistance. We investigated the role of a recently identified drug-resistance gene, taxol-resistant gene 1 (Txr1), in oxaliplatin resistance. A retrospective study based on banked tissue was carried out. We collected clinical data from 95 patients with stage II–III GC who were treated with radical D2 surgery and standardized first-line chemotherapy with oxaliplatin; paraffin blocks of their tumor specimens were prepared for a tissue microarray in which Txr1 expression was analyzed immunohistochemically and compared with their clinical data and their 3-year disease-free survival (DFS) rate. The human GC cell line, SGC7901, was developed into the oxaliplatin-resistant cell line, SGC7901/L-OHP, using slowly increased oxaliplatin concentrations over 6 months. The relationship between Txr1 expression and drug-resistance of oxaliplatin in GC was studied with drug intervention, gene silencing technology, real-time PCR and Western blot analysis. Of the 95 patients with GC, those with TXR1 GC had longer postoperative 3-year DFS (77.8 %) than those with TXR1+ GC (52.9 %). In oxaliplatin-resistant SGC7901/L-OHP cells, the main expression location of Txr1 shifted from the nucleus to cytoplasm, and both the mRNA and protein expression of Txr1 were higher than that of the parental cells, whereas expression of thrombospondin-1 (TSP1) decreased. When the Txr1 gene was silenced, TSP1 expression increased and the oxaliplatin resistance was significantly reduced in SGC7901/L-OHP cells. Changed Txr1 expression in GC affects the efficacy of oxaliplatin-based chemotherapy. Increased Txr1 expression decreases TSP1 expression and inhibits apoptosis. Txr1 could be a target in reversing oxaliplatin resistance in GC.
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Metadata
Title
Txr1: an important factor in oxaliplatin resistance in gastric cancer
Authors
Jingtao Bi
Zhigang Bai
Xuemei Ma
Jianning Song
Yantong Guo
Jingming Zhao
Xin Yi
Shiwei Han
Zhongtao Zhang
Publication date
01-02-2014
Publisher
Springer US
Published in
Medical Oncology / Issue 2/2014
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-013-0807-1

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