The high mortality rate associated with gastric cancer(GC)has resulted in an urgent need to identify novel therapeutic targets for GC.This study aimed to investigate whether GAIP interacting protein,C terminus 1(GIPC1...The high mortality rate associated with gastric cancer(GC)has resulted in an urgent need to identify novel therapeutic targets for GC.This study aimed to investigate whether GAIP interacting protein,C terminus 1(GIPC1)represents a therapeutic target and its regulating mechanism in GC.GIPC1 expression was elevated in GC tissues,liver metastasis tissues,and lymph node metastases.GIPC1 knockdown or GIPC1 blocking peptide blocked the platelet-derived growth factor receptor(PDGFR)/PI3K/AKT signaling pathway,and inhibited the proliferation and migration of GC cells.Conversely,GIPC1 overexpression markedly activated the PDGFR/PI3K/AKT signaling pathway,and promoted GC cell proliferation and migration.Furthermore,platelet-derived growth factor subunit BB(PDGF-BB)cytokines and the AKT inhibitor attenuated the effect of differential GIPC1 expression.Moreover,GIPC1 silencing decreased tumor growth and migration in BALB/c nude mice,while GIPC1 overexpression had contrasting effects.Taken together,our findings suggest that GIPC1 functions as an oncogene in GC and plays a central role in regulating cell proliferation and migration via the PDGFR/PI3K/AKT signaling pathway.展开更多
目的:探讨PDGFR-αASODN对视网膜的毒性作用。方法:选择健康成年有色家兔24只,随机分为4组,每组6只;4组兔子3组右眼玻璃体分别注射0.1 m L不同浓度的PDGFR-αASODN/lipofectamine TM 2000溶液,另外1组注射0.1 m L平衡盐溶液作为对照组;...目的:探讨PDGFR-αASODN对视网膜的毒性作用。方法:选择健康成年有色家兔24只,随机分为4组,每组6只;4组兔子3组右眼玻璃体分别注射0.1 m L不同浓度的PDGFR-αASODN/lipofectamine TM 2000溶液,另外1组注射0.1 m L平衡盐溶液作为对照组;4组兔子的左眼不注药。于注药后第1、7、14及28天,对4组兔子的右眼行裂隙灯、间接检眼镜、视网膜电图(ERG)检查;第28天,取4组兔子的眼球,对视网膜组织进行光镜HE、免疫组化及透射电镜的观察。结果:裂隙灯、间接检眼镜检查,各组在各个检查时间点均未发现异常。ERG b波振幅,实验组与对照组比较差异无显著性。注药后第28天,光镜下HE和免疫组化检查,各组视网膜组织均未发现任何病理变化。注药后第28天电镜检查,D组视网膜感光细胞:部分膜盘间隙扩张,部分膜盘融合,少数细胞核周围间隙略增大,其细胞核形态略不规则。结论:玻璃体内注射0.1 m L PDGFR-αASODN/lip2000时,PDGFR-αASODN的浓度≤1.5μmol/L是较为安全的。展开更多
基金supported by the Natural Science Foundation of Xiamen City(3502Z20227307)the National Natural Science Foundation of China(81472458,82372809)the Special Fund for Public Welfare Research Institutes of Fujian Province(2023R1001001,2023R1001003,2023R1035).
文摘The high mortality rate associated with gastric cancer(GC)has resulted in an urgent need to identify novel therapeutic targets for GC.This study aimed to investigate whether GAIP interacting protein,C terminus 1(GIPC1)represents a therapeutic target and its regulating mechanism in GC.GIPC1 expression was elevated in GC tissues,liver metastasis tissues,and lymph node metastases.GIPC1 knockdown or GIPC1 blocking peptide blocked the platelet-derived growth factor receptor(PDGFR)/PI3K/AKT signaling pathway,and inhibited the proliferation and migration of GC cells.Conversely,GIPC1 overexpression markedly activated the PDGFR/PI3K/AKT signaling pathway,and promoted GC cell proliferation and migration.Furthermore,platelet-derived growth factor subunit BB(PDGF-BB)cytokines and the AKT inhibitor attenuated the effect of differential GIPC1 expression.Moreover,GIPC1 silencing decreased tumor growth and migration in BALB/c nude mice,while GIPC1 overexpression had contrasting effects.Taken together,our findings suggest that GIPC1 functions as an oncogene in GC and plays a central role in regulating cell proliferation and migration via the PDGFR/PI3K/AKT signaling pathway.
文摘目的:探讨PDGFR-αASODN对视网膜的毒性作用。方法:选择健康成年有色家兔24只,随机分为4组,每组6只;4组兔子3组右眼玻璃体分别注射0.1 m L不同浓度的PDGFR-αASODN/lipofectamine TM 2000溶液,另外1组注射0.1 m L平衡盐溶液作为对照组;4组兔子的左眼不注药。于注药后第1、7、14及28天,对4组兔子的右眼行裂隙灯、间接检眼镜、视网膜电图(ERG)检查;第28天,取4组兔子的眼球,对视网膜组织进行光镜HE、免疫组化及透射电镜的观察。结果:裂隙灯、间接检眼镜检查,各组在各个检查时间点均未发现异常。ERG b波振幅,实验组与对照组比较差异无显著性。注药后第28天,光镜下HE和免疫组化检查,各组视网膜组织均未发现任何病理变化。注药后第28天电镜检查,D组视网膜感光细胞:部分膜盘间隙扩张,部分膜盘融合,少数细胞核周围间隙略增大,其细胞核形态略不规则。结论:玻璃体内注射0.1 m L PDGFR-αASODN/lip2000时,PDGFR-αASODN的浓度≤1.5μmol/L是较为安全的。
