胃肠道间质瘤伊马替尼耐药中的细胞内浓度与转运体

Intracellular concentration and transporters in imatinib resistance of gastrointestinal stromal tumor.

作者信息

Zhang Qiang, Li Zheng, Xu Kangjing, Qian Yi, Chen Ming, Sun Luning, Song Shanshan, Huang Xiaoxu, He Zhongyuan, Li Fengyuan, Zhang Diancai, Yang Li, Wang Yongqing, Xu Hao, Xu Zekuan

机构信息

a Department of General Surgery , The First Affiliated Hospital of Nanjing Medical University , Nanjing , China.

b Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment , Jiangsu Collaborative Innovation Center for Cancer Personalized Medical University , Nanjing , China.

出版信息

Scand J Gastroenterol. 2019 Feb;54(2):220-226. doi: 10.1080/00365521.2019.1577488. Epub 2019 Mar 17.

DOI:10.1080/00365521.2019.1577488

PMID:30879345

Abstract

BACKGROUND

We aimed to investigate the role of intracellular imatinib concentration in drug resistance and the expression of candidate drug transporters in gastrointestinal stromal tumor (GIST) cell lines.

METHOD

The imatinib concentrations were measured by the liquid chromatography-tandem mass spectrometry (LC-MS/MS). The expression of candida te drug transporters was detected by qRT-PCR.

RESULTS

The tissue imatinib concentrations in imatinib resistant patients were significantly lower than that of sensitive patients (p < .05). Compared with parental cell lines, the intracellular imatinib concentration was notably lower in imatinib resistant GIST cell lines. For candidate transporters, MRP1 and BCRP were overexpressed in resistant GIST cell lines.

CONCLUSION

The intracellular imatinib concentration may play a crucial role in imatinib resistance and the intracellular differences of imatinib concentration may be induced by the upregulation of efflux transporters. Our study highlights the importance of intracellular imatinib concentration and the potential of using imatinib transporters as therapeutic targets for patients with GIST.

摘要