Qiang Zhang1,2, Zheng Li1,2, Kangjing Xu1,2, Yi Qian3, Ming Chen1,2, Luning Sun3, Shanshan Song4, Xiaoxu Huang1,5, Zhongyuan He1,2, Fengyuan Li1,2, Diancai Zhang1,2, Li Yang1,2, Yongqing Wang3, Hao Xu1,2, Zekuan Xu1,2. 1. a Department of General Surgery , The First Affiliated Hospital of Nanjing Medical University , Nanjing , China. 2. b Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment , Jiangsu Collaborative Innovation Center for Cancer Personalized Medical University , Nanjing , China. 3. c Research Division of Clinical Pharmacology , The First Affiliated Hospital of Nanjing Medical University , Nanjing , China. 4. d Department of Pathology , Xuzhou Medical University Affiliated Hospital of Lianyungang , Lianyungang , China. 5. e Department of Gastrointestinal Surgery , The First Affiliated Yijishan Hospital of Wannan Medical College , Anhui , Wuhu , China.
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.
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.