Intracellular concentration and transporters in imatinib resistance of gastrointestinal stromal tumor

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.

Keywords:

• Gastrointestinal stromal tumor
• resistance
• intracellular imatinib concentration
• transporters

Disclosure statement

The authors have no conflicts of interest of financial ties to disclose.

Additional information

Funding

This work was sponsored by funds from Natural Science Foundation of Province (BK20141493, to H. XU), Jiangsu Key Medical Discipline (General Surgery; ZDXKA2016005), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD, JX10231801), the Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative, Nanjing Medical University (all to Z. Xu), the National Natural Science Foundation of China (81503160, to L. Sun), and Construction Program of Jiangsu Provincial Clinical Research Center Support System (BL2014084).