Effects of taxol resistance gene 1 on the cisplatin response in gastric cancer

被引:7
作者
Duan, Shuquan
Yin, Jie
Bai, Zhigang [1 ,2 ]
Zhang, Zhongtao [1 ,2 ]
机构
[1] Capital Med Univ, Beijing Friendship Hosp, Dept Gen Surg, Beijing Key Lab Canc Invas & Metastasis Res, 95 Yongan Rd, Beijing 100050, Peoples R China
[2] Natl Clin Res Ctr Digest Dis, 95 Yongan Rd, Beijing 100050, Peoples R China
基金
中国国家自然科学基金;
关键词
cisplatin; chemoresistance; taxol resistance gene 1; gastric cancer; apoptosis; DRUG-RESISTANCE; EXPRESSION; CHEMOTHERAPY; TXR1; THROMBOSPONDIN-1; MECHANISMS; APOPTOSIS; SURVIVAL; TAXANES; CELLS;
D O I
10.3892/ol.2018.8390
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cisplatin is used to treat multiple types of solid tumor, including gastric cancer. Although cisplatin initially exhibits good efficacy, therapeutic failure often occurs owing to the development of chemoresistance. To the best of our knowledge, the underlying mechanism of cisplatin resistance remains unknown. The aim of the present study was to assess whether taxol resistance gene 1 (TXR1) has a role in cisplatin response in gastric cancer. The expression of TXR1 in fresh-frozen tissues of patients with gastric cancer who were sensitive or resistance to cisplatin was assessed. The level of TXR1 expression was significantly higher in cisplatin-resistant specimens than that in cisplatin-sensitive specimens. Next, the gastric cancer SGC-7901 cell line was exposed to cisplatin to establish a cisplatin-resistance subline, termed SGC-7901/DDP, which exhibited a 6-fold increases in the level of resistance. TXR1 expression was elevated in SGC-7901/DDP cells. Overexpression of TXR1 induced cisplatin resistance in SGC-7901 cells. Downregulation of TXR1 reversed the drug resistance caused by elevation of TXR1 expression in SGC-7901/DDP cells. Animal experiments proved the effect of TXR1 in inducing cisplatin resistance in vivo. Further investigation revealed that TXR1 regulated cisplatin resistance via apoptosis. In conclusion, TXR1 is worthy of further in-depth study as a potential therapeutic target in patients with gastric cancer.
引用
收藏
页码:8287 / 8294
页数:8
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