细胞内伊马替尼浓度在胃肠道间质瘤耐药过程中的作用

目的探讨细胞内伊马替尼浓度与胃肠道间质瘤（GIST）耐药性的关系。 方法随机选择南京医科大学第一附属医院2014年12月至2016年4月伊马替尼耐药和敏感的进展期GIST患者各4例，采用液相色谱-串联质谱法（LC-MS/MS）检测细胞内外、组织内与血浆伊马替尼浓度。苏木精-伊红染色和免疫组织化学法观察细胞的形态特征。 结果伊马替尼耐药患者组织内药物浓度比敏感患者的组织内药物浓度低（P<0.05）。与亲代敏感细胞株相比，伊马替尼耐药GIST细胞株中细胞内伊马替尼浓度显著降低，同时细胞形态也发生了变化。 结论低细胞内药物浓度可能是伊马替尼耐药的重要原因，细胞内伊马替尼浓度可能是治疗GIST过程中的关键要素。

Role of intracellular imatinib concentration in drug resistance of gastrointestinal stromal tumor

Objective To investigate the relationship between intracellular imatinib concentration and drug resistance of gastrointestinal stromal tumor(GIST).Methods Eight advanced GIST patients with imatinib-resistant and-susceptible were randomly selected from the First Affiliated Hospital of Nanjing Medical University from December 2014 to April 2016.Concentrations of imatinib in cells,tissues and plasma were measured by liquid chromatography-tandem mass spectrometry(LC-MS/MS).The morphological characteristics of cells were observed by hematoxylin-eosin staining and immunohistochemistry.Results The imatinib concentration in tissues of imatinib-resistant patients was lower than that of imatinib-susceptible patients(P<0.05).Compared with parental sensitive cell lines,imatinib concentration of imatinib-resistant cell lines decreased significantly and cell morphology was also changed.Conclusion Low intracellular drug concentration may be an important reason of imatinib resistance,and intracellular imatinib concentration may be a key point in the treatment of GIST.