FRBI对子宫癌相关基因FHIT、PTEN和ARID1A表达作用研究

FRBI Depressed FHIT,PTEN and ARID1A Levels of Serum and Uteri in Female Mice

目的:探讨促卵泡激素受体结合抑制剂(FRBI)对子宫癌发生相关基因FHIT、PTEN、ARID1A血清浓度及子宫组织中表达水平的影响.方法:150只21日龄雌鼠随机分为4个FRBI实验组和对照组(CG).FRBI-1、FRBI-2、FRBI-3和FRBI-4组小鼠分别肌肉注射10、20、30、40 mg/kg的FRBI,连续注射5天,CG组肌肉注射生理盐水0.2 mL.用ELISA、qRT-PCR法和Western-blot检测血清FHIT、PTEN、ARID1A含量及子宫组织中表达水平.结果:FRBI-3组血清FHIT浓度和FRBI-4组血清ARID1A浓度均显著高于CG组(P<0.05).FRBI-3和FRBI-4组子宫组织FHIT mRNA的水平在第20、30天均高于CG组(P<0.05,P<0.01).第30天,4个FRBI实验组FHIT蛋白表达水平分别比对照组提高28.03%、69.82%、118.33%和99.46%.FRBI剂量与血清FHIT,PTEN和ARID1A浓度及子宫表达水平呈正相关(P<0.05).血清FHIT、PTEN和ARID1A浓度与其在子宫组织中表达水平也呈正相关.结论:FRBI增加血清FHIT和ARID1A的含量,能提高小鼠子宫组织FHIT、PTEN、ARID1A蛋白和FHIT mRNA表达水平.本研究将为控制子宫癌的发生和靶向治疗提供理论依据.

Objective In order to explore the interaction of follicle stimulating hormone receptor binding inhibitor(FRBI)on fragile histidine triad(FHIT),phosphatase and tensin homolog(PTEN)and AT-rich interactive domain-containing protein 1A(ARID1A)and estrogen receptorβ(ERβ)serum levels and expression levels in uterine tissues.Methods 150 female 21-day-old mice were randomly divided into four FRBI experimental groups and control group(CG).FRBI-1,FRBI-2,FRBI-3,and FRBI-4 groups were intramuscularly injected continuously for 5 days with FRBI of 10,20,30,and 40 mg/kg,respectively.CG was intramuscularly injected with 0.2 mL of normal saline.The expression levels of FHIT,PTEN,ARID1A in serum and uterine tissue were detected by ELISA kit,qRT-PCR method and Western blotting,respectively.Results Serum FHIT concentrations of FRBI-3 group and ARID1A of FRBI-4 group were significantly higher than those of CG(P<0.05).FHIT mRNA levels of FRBI-3 and FRBI-4 groups were greater than that in CG on days 20 and 30(P<0.05 or P<0.01).On day 30,expression levels of FHIT proteins in four FRBI groups were increased by 28.03%,69.82%,118.33%and 99.46%,respectively as compared to CG.FRBI doses had positive correlations to serum and uterine levels of FHIT,PTEN and ARID1A(P<0.05).Serum contents of FHIT,PTEN and ARID1A had positive correlations with uterine expressions of FHIT,PTEN and ARID1A proteins,respectively.Conclusions FRBI promoted the production of serum FHIT and ARID1A,and accelerated the expression levels of FHIT,PTEN,ARID1A protein and FHIT mRNA in mice uteri.