BACKGROUND Gastrointestinal stromal tumors(GISTs)are typical gastrointestinal tract neoplasms.Imatinib is the first-line therapy for GIST patients.Drug resistance limits the long-term effectiveness of imatinib.The reg...BACKGROUND Gastrointestinal stromal tumors(GISTs)are typical gastrointestinal tract neoplasms.Imatinib is the first-line therapy for GIST patients.Drug resistance limits the long-term effectiveness of imatinib.The regulatory effect of insulin-like growth factor 2(IGF2)has been confirmed in various cancers and is related to resistance to chemotherapy and a worse prognosis.AIM To further investigate the mechanism of IGF2 specific to GISTs.METHODS IGF2 was screened and analyzed using Gene Expression Omnibus(GEO:GSE225819)data.After IGF2 knockdown or overexpression by transfection,the phenotypes(proliferation,migration,invasion,apoptosis)of GIST cells were characterized by cell counting kit 8,Transwell,and flow cytometry assays.We used western blotting to evaluate pathway-associated and epithelial-mesenchymal transition(EMT)-associated proteins.We injected transfected cells into nude mice to establish a tumor xenograft model and observed the occurrence and metastasis of GIST.RESULTS Data from the GEO indicated that IGF2 expression is high in GISTs,associated with liver metastasis,and closely related to drug resistance.GIST cells with high expression of IGF2 had increased proliferation and migration,invasiveness and EMT.Knockdown of IGF2 significantly inhibited those activities.In addition,OEIGF2 promoted GIST metastasis in vivo in nude mice.IGF2 activated IGF1R signaling in GIST cells,and IGF2/IGF1R-mediated glycolysis was required for GIST with liver metastasis.GIST cells with IGF2 knockdown were sensitive to imatinib treatment when IGF2 overexpression significantly raised imatinib resistance.Moreover,2-deoxy-D-glucose(a glycolysis inhibitor)treatment reversed IGF2 overexpressionmediated imatinib resistance in GISTs.CONCLUSION IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.展开更多
为探究超数排卵对家兔早期胚胎发育及IGF1、EGF基因表达的影响,本实验选取成年健康家兔48只,随机分为超排组和对照组,对超排组家兔注射70 IU PMSG+100 IU hCG进行超排处理,观察超排处理对排卵、胚胎体外发育的影响,并通过qRT-PCR分析IGF...为探究超数排卵对家兔早期胚胎发育及IGF1、EGF基因表达的影响,本实验选取成年健康家兔48只,随机分为超排组和对照组,对超排组家兔注射70 IU PMSG+100 IU hCG进行超排处理,观察超排处理对排卵、胚胎体外发育的影响,并通过qRT-PCR分析IGF1和EGFmRNA在早期胚胎中的表达差异。结果显示:超排组家兔的平均充血卵泡数、平均排卵点数、平均胚胎收集数和畸形率均显著高于对照组,4-细胞期和8-细胞期的胚胎发育率显著低于对照组。无论是对照组还是超排组,IGF1基因均在4-细胞期表达量最高,而EGF基因在2-细胞期表达量最高。超排组中,IGF1基因在2-细胞期胚胎中的表达量显著低于对照组,在4-细胞期和8-细胞期胚胎中与对照组相比差异不显著,而EGF基因在2-细胞期胚胎中的表达量显著高于对照组,在4-细胞期和8-细胞期胚胎中则显著低于对照组。综上可知,外源促性腺激素可能通过改变IGF1和EGF在早期胚胎中的表达量而影响家兔早期胚胎的发育。展开更多
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)are typical gastrointestinal tract neoplasms.Imatinib is the first-line therapy for GIST patients.Drug resistance limits the long-term effectiveness of imatinib.The regulatory effect of insulin-like growth factor 2(IGF2)has been confirmed in various cancers and is related to resistance to chemotherapy and a worse prognosis.AIM To further investigate the mechanism of IGF2 specific to GISTs.METHODS IGF2 was screened and analyzed using Gene Expression Omnibus(GEO:GSE225819)data.After IGF2 knockdown or overexpression by transfection,the phenotypes(proliferation,migration,invasion,apoptosis)of GIST cells were characterized by cell counting kit 8,Transwell,and flow cytometry assays.We used western blotting to evaluate pathway-associated and epithelial-mesenchymal transition(EMT)-associated proteins.We injected transfected cells into nude mice to establish a tumor xenograft model and observed the occurrence and metastasis of GIST.RESULTS Data from the GEO indicated that IGF2 expression is high in GISTs,associated with liver metastasis,and closely related to drug resistance.GIST cells with high expression of IGF2 had increased proliferation and migration,invasiveness and EMT.Knockdown of IGF2 significantly inhibited those activities.In addition,OEIGF2 promoted GIST metastasis in vivo in nude mice.IGF2 activated IGF1R signaling in GIST cells,and IGF2/IGF1R-mediated glycolysis was required for GIST with liver metastasis.GIST cells with IGF2 knockdown were sensitive to imatinib treatment when IGF2 overexpression significantly raised imatinib resistance.Moreover,2-deoxy-D-glucose(a glycolysis inhibitor)treatment reversed IGF2 overexpressionmediated imatinib resistance in GISTs.CONCLUSION IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.
文摘为探究超数排卵对家兔早期胚胎发育及IGF1、EGF基因表达的影响,本实验选取成年健康家兔48只,随机分为超排组和对照组,对超排组家兔注射70 IU PMSG+100 IU hCG进行超排处理,观察超排处理对排卵、胚胎体外发育的影响,并通过qRT-PCR分析IGF1和EGFmRNA在早期胚胎中的表达差异。结果显示:超排组家兔的平均充血卵泡数、平均排卵点数、平均胚胎收集数和畸形率均显著高于对照组,4-细胞期和8-细胞期的胚胎发育率显著低于对照组。无论是对照组还是超排组,IGF1基因均在4-细胞期表达量最高,而EGF基因在2-细胞期表达量最高。超排组中,IGF1基因在2-细胞期胚胎中的表达量显著低于对照组,在4-细胞期和8-细胞期胚胎中与对照组相比差异不显著,而EGF基因在2-细胞期胚胎中的表达量显著高于对照组,在4-细胞期和8-细胞期胚胎中则显著低于对照组。综上可知,外源促性腺激素可能通过改变IGF1和EGF在早期胚胎中的表达量而影响家兔早期胚胎的发育。
