胰岛素通过Akt和Erk信号通路对甲状腺乳头状癌细胞的增殖作用  

The proliferative effects of insulin on papillary thyroid carcinoma cells through Akt and Erk signaling

作　　者：姚侃男 盛晓理 姚定国[1] Yao Kannan

机构地区：[1]浙江中医药大学附属第一医院,310006 [2]浙江大学医学院附属第一医院,310001

出　　处：《浙江临床医学》2022年第4期482-486,共5页Zhejiang Clinical Medical Journal

基　　金：浙江中医药大学校级科研基金项目(2018ZY07)。

摘　　要：目的探讨胰岛素及其类似物通过Akt和Erk信号通路对甲状腺乳头状癌细胞(PTC-1s)的增殖作用。方法构建针对人IGF1R基因的LV-NC-GFP及RNA干扰慢病毒载体,感染PTC-1s,建立IGF1R正常表达及低表达的PTC-1s细胞模型。体外培养IGF1R正常表达及低表达PTC-1s细胞,分别设置为空白对照组、IGF1R正常表达PTC-1s细胞模型组和IGF1R低表达PTC-1s细胞模型组。通过CCK8法观察常规人胰岛素和甘精胰岛素对细胞的增殖作用,运用Western Blot法检测两种胰岛素分别干预两种PTC-1s后的IGF1R下游Akt和Erk信号通路蛋白p-Akt和p-Erk的表达。结果人胰岛素和甘精胰岛素对IGF1R正常表达的PTC-1s细胞的促细胞增殖作用呈时间依赖性,人胰岛素和甘精胰岛素相较于空白对照组,有明显的促细胞增殖作用(P<0.05)。人胰岛素和甘精胰岛素均不能促使IGF1R低表达细胞增殖,与空白对照组比较无明显统计学差异(P>0.05)。人胰岛素和甘精胰岛素能促使IGF1R正常表达细胞Akt和Erk磷酸化,与空白对照组比较,差异均有统计学意义(P<0.05)。而且甘精胰岛素的促Akt磷酸化作用强于人胰岛素,人胰岛素组促Erk磷酸化作用强于甘精胰岛素组,差异均有统计学意义(P<0.05)。人胰岛素和甘精胰岛素均不能使IGF1R低表达细胞Akt和Erk磷酸化,与空白对照组比较,差异无统计学意义(P>0.05)。结论人胰岛素和甘精胰岛素通过IGF1R激活Akt和Erk信号通路,促进PTC-1s细胞增殖,且甘精胰岛素的促PTC-1s细胞增殖作用强于人胰岛素。Objective To investigate the effects of insulin and its analogues on the proliferation of papillary thyroid carcinoma cells(PTC-1s)through Akt and Erk signaling pathways.Methods Construct LV-NC-GFP and RNA interference lentivirus of human IGF1R gene,infect PTC-1s,and establish PTC-1s cell models with normal and low expression of IGF1R.Culture PTC-1 cells with normal and low expression of IGF1R in vitro,and divide into the blank control group,the PTC-1 cell group with normal expression of IGF1R and PTC-1 cell group with low expression of IGF1R.CCK8 method was used to observe the proliferation of the PTC-1 cells dealt with human insulin and insulin glargine.The phosphorylation of IGF1R and the expression of p-Akt and p-Erk after interventions of human insulin and insulin glargine were detected by Western Blot.Results Human insulin and insulin glargine had a time-dependent effect on the proliferation of PTC-1 cells that were normal expression of IGF1R,and the effect of human insulin and insulin glargine was significantly greater than that of the blank control group(P<0.05).Human insulin and insulin glargine could not promote the proliferation of cells with low expression of IGF1R,and there was no significant difference compared with the blank control group.Human insulin and insulin glargine could promote the phosphorylation of Akt and Erk of IGF1R cells with normal expression,and the differences were statistically significant compared with blank control group(P<0.05).The rates of abortion and premature delivery in group C were lower than those in group A and B,and the duration of abnormal vaginal bleeding was shorter than those in group A and B,while the levels of bloodβ-HCG,estradiol and progesterone were higher than those in group A and B,and the differences were statistically significant(P<0.05).There was no significant difference in the incidence of adverse reactions among the three groups(P>0.05).Conclusion Low dose Aspirin combined with low molecular weight heparin sodium treatment can not only effectively im

关 键 词：甲状腺乳头状癌 胰岛素 甘精胰岛素 胰岛素样生长因子1类受体 Akt信 号通路 ERK信号通路 

分 类 号：R73[医药卫生—肿瘤]