甲磺酸伊马替尼和苹果酸舒尼替尼联合应用对胃肠道间质瘤细胞迁移和侵袭能力的影响  

Effects of combined imatinib mesylate and sunitinib malate therapy on migration and invasion of gastrointestinal stromal tumor cells

作　　者：李祉剑 王文思[2] 马鸿滢 贾钧凯 张天彪[3] 赵滢[1] LI Zhijian;WANG Wensi;MA Hongying;JIA Junkai;ZHANG Tianbiao;ZHAO Ying(Department of Gastrointestinal Nutritional Surgery,Shengjing Hospital of China Medical University,Shenyang 110004,China;Department of National Immunization Program,Liaoning Provincial Centre for Disease Control and Prevention,Shenyang 110005,China;Department of Biochemistry and Molecular Biology,School of Life Sciences,China Medical University,Shenyang 110122,China)

机构地区：[1]中国医科大学附属盛京医院胃肠营养外科,沈阳110004 [2]辽宁省疾病预防控制中心免疫规划所,沈阳110005 [3]中国医科大学生命科学学院生物化学与分子生物学教研室,沈阳110122

出　　处：《中国医科大学学报》2025年第3期193-198,共6页Journal of China Medical University

基　　金：国家自然科学基金(62373370,61973316)。

摘　　要：目的探讨甲磺酸伊马替尼和苹果酸舒尼替尼对胃肠道间质瘤(GIST)细胞迁移和侵袭能力的影响。方法GIST细胞原代培养鉴定后,利用原子力显微镜(AFM)观察细胞形态表征;给予药物作用后,用实时定量PCR检测PI3K/AKT信号通路相关基因表达的变化,用AFM检测相关分子结合力的变化;用划痕实验、Transwell实验和流式细胞术测定细胞迁移、侵袭能力和凋亡的变化。结果AFM成像提示伪足平铺在GIST细胞周围,GIST细胞具有易于转移的特征;单独应用甲磺酸伊马替尼或苹果酸舒尼替尼后,PI3K/AKT信号通路相关基因表达明显降低,GIST细胞表面表皮生长因子受体(EGFR)密度下降,与表皮生长因子(EGF)的分子结合力下降,联合用药时上述变化更加明显;单独用药时,GIST细胞侵袭和迁移能力均显著下降,而联合用药对GIST迁移和侵袭的抑制更为显著。结论甲磺酸伊马替尼和苹果酸舒尼替尼单独用药均能显著抑制PI3K/AKT信号通路相关基因表达,降低GIST细胞表面EGFR密度,并减弱其与EGF的分子结合力,减弱GIST细胞迁移和侵袭的能力,联合用药比单独用药效果更显著。Objective To investigate the effects of imatinib mesylate and sunitinib malate on the migration and invasion of gastrointestinal stromal tumor(GIST)cells.Methods After identifying primary-cultured GIST cells,their morphology was characterized using atomic force microscopy(AFM).Changes in the expression of genes related to the PI3K/AKT signaling pathway were analyzed using quantitative real-time PCR following drug treatments.Changes in the binding of related molecules were detected using AFM,and alterations in cell migration,invasive ability,and apoptosis were determined using scratch assay,Transwell assay,and flow cytometry,respectively.Results AFM imaging showed that pseudopods were flatly spread around the GIST cells,indicating characteristics consistent with easy metastasis.Administration of either imatinib or sunitinib significantly reduced the expression of genes related to the PI3K/AKT signaling pathway,the density of epidermal growth factor receptor(EGFR)on the surface of GIST cells,and molecular binding force with EGF.These changes were more pronounced with the combination treatment.Correspondingly,the invasive and migratory abilities of GIST cells were significantly reduced when either drug was administered alone and the inhibitory effect was more significant when the drugs were combined.Conclusion Both imatinib and sunitinib can significantly inhibit the expression of genes related to the PI3K/AKT signaling pathway,reduce the density of EGFR on the surface of GIST cells,and attenuate their molecular binding to EGF,thereby reducing the migration and invasion of GIST cells.However,the combination of these two drugs has a more significant effect.

关 键 词：胃肠道间质瘤 甲磺酸伊马替尼 苹果酸舒尼替尼 联合用药 迁移 侵袭 

分 类 号：R735[医药卫生—肿瘤]