核心蛋白聚糖、甲磺酸伊马替尼、苹果酸舒尼替尼对胃肠道间质瘤细胞恶性表型的影响  

Effects of decorin,imatinib mesylate,and sunitinib malate on the malignant phenotype of gastrointestinal stromal tumor cells

作　　者：唐珊 贾钧凯 马鸿滢 赵滢[2] 张天彪[3] TANG Shan;JIA Junkai;MA Hongying;ZHAO Ying;ZHANG Tianbiao(Department of Anesthesiology,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China;Department of Gastrointestinal Nutrition,Shengjing Hospital of China Medical University,Shenyang 110004,China;Department of Biochemistry and Molecular Biology,School of Life Sciences,China Medical University,Shenyang 110122,China)

机构地区：[1]上海交通大学医学院附属第九人民医院麻醉科,上海200011 [2]中国医科大学附属盛京医院胃肠营养外科,沈阳110004 [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》2024年第11期961-966,共6页Journal of China Medical University

基　　金：国家自然科学基金(61973316)。

摘　　要：目的探究核心蛋白聚糖(DCN)、甲磺酸伊马替尼、苹果酸舒尼替尼对胃肠道间质瘤(GIST)细胞恶性表型的影响及其分子机制。方法采用Western blotting检测过表达DCN以及甲磺酸伊马替尼和苹果酸舒尼替尼单独或联合用药后,GIST细胞(GIST-882)中DCN及其下游相关蛋白表达水平的变化。采用CCK-8实验、划痕实验、Transwell实验验证过表达DCN以及甲磺酸伊马替尼和苹果酸舒尼替尼单独或联合用药后,GIST-882细胞增殖、迁移和侵袭能力的变化。结果与对照组比较,过表达DCN以及甲磺酸伊马替尼和苹果酸舒尼替尼单独或联合用药后,GIST-882细胞中DCN蛋白表达水平升高,表皮生长因子受体(EGFR)、磷酸化EGFR(p-EGFR)、胞外信号调节激酶1/2(ERK1/2)、磷酸化ERK1/2(p-ERK1/2)蛋白表达水平降低,细胞增殖、迁移和侵袭能力显著降低。结论过表达DCN以及甲磺酸伊马替尼或苹果酸舒尼替尼单独或联合用药,可以通过下调EGFR的表达参与MAPK信号传导通路,进而调控GIST细胞的增殖、迁移和侵袭能力。Objective To investigate the effects and molecular mechanisms of decorin(DCN),imatinib mesylate,and sunitinib malate on the malignant phenotype of gastrointestinal stromal tumor cells.Methods Western blotting was used to detect changes in the expression of DCN and its downstream proteins after DCN overexpression and treatment with imatinib mesylate and sunitinib malate alone or in combination in gastrointestinal stromal tumor cells(GIST-882).Cell counting kit-8,scratch,and Transwell assays were performed to validate the changes in cell proliferation,migration,and invasion abilities after DCN overexpression and treatment with imatinib mesylate and sunitinib malate alone or in combination in GIST-882 cells.Results Compared with the control group,DCN overexpression and treatment with imatinib mesylate and sunitinib malate alone or in combination in GIST-882 cells increased the expression levels of DCN protein,decreased the expression levels of epidermal growth factor receptor(EGFR),phosphorylated EGFR(p-EGFR),extracellular signal-regulated kinase 1/2(ERK1/2),and phosphorylated ERK1/2(p-ERK1/2)proteins,and significantly reduced cell proliferation,migration,and invasion abilities.Conclusion DCN overexpression and treatment with imatinib mesylate and sunitinib malate alone or in combination affect the MAPK signaling pathway by downregulating the expression of EGFR,thereby regulating the proliferation,migration,and invasion abilities of gastrointestinal stromal tumor cells.

关 键 词：胃肠道间质瘤 核心蛋白聚糖 表皮生长因子受体 甲磺酸伊马替尼 苹果酸舒尼替尼 

分 类 号：R735[医药卫生—肿瘤]