联合靶向抑制成纤维细胞生长因子受体和哺乳动物雷帕霉素靶蛋白在卵巢癌发生发展中的作用机制  

Mechanism of combined targeted inhibition of fibroblast growth factor receptor and mammalian target of rapamycin in the occurrence and development of ovarian cancer

作　　者：李均[1] 汤亚兰[1] 唐方祥 徐凡[1] 唐英[1] 胡辉权[1] 罗岳西[1] Li Jun;Tang Yalan;Tang Fangxiang;Xu Fan;Tang Ying;Hu Huiquan;Luo Yuexi(Department of Gynecology,the Second Affiliated Hospital of North Sichuan Medical College,Nanchong Central Hospital,Sichuan,Nanchong 637000,China)

机构地区：[1]川北医学院第二临床医学院南充市中心医院妇科,四川南充637000

出　　处：《中国医学前沿杂志（电子版）》2021年第3期99-103,共5页Chinese Journal of the Frontiers of Medical Science(Electronic Version)

基　　金：四川省科学技术厅项目基金(16JC0273);南充市校科技战略合作专项(NSMC20170464)。

摘　　要：目的探讨联合靶向抑制成纤维细胞生长因子受体(fibroblast growth factor receptor,FGFR)和哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)在卵巢癌发生发展中的作用机制。方法收集80只雌性SD大鼠,其中60只建立卵巢癌大鼠模型并随机分为实验1组(注射FGFR抑制剂,20只)、实验2组(注射mTOR抑制剂,20只)、联合组(注射mTOR抑制剂和FGFR抑制剂,20只),另20只大鼠记为常规组(常规饲养并注射生理盐水),比较各组大鼠肿瘤微环境相关因子[细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)、蛋白激酶R样内质网激酶(protein kinase R-like endoplasmic reticulum kinase,pERK)、低氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)]mRNA相对表达量和蛋白相对表达量。而后将模型大鼠处死取得组织液与巨噬细胞共培养,观察实验1组、实验2组、联合组卵巢癌细胞增殖率和凋亡率。结果联合组、常规组大鼠ERK、pERK、HIF-1α的mRNA相对表达量和蛋白表达水平均显著低于实验1组、实验2组(均P<0.05),联合组与常规组大鼠以上指标比较差异均无统计学意义(均P>0.05)。干预后,卵巢癌细胞增殖率依次为:联合组<实验2组<实验1组(均P<0.05);卵巢癌细胞凋亡率依次为:联合组>实验2组>实验1组(均P<0.05)。结论联合靶向抑制FGFR和mTOR可明显降低卵巢癌增殖而有效促进其癌细胞凋亡,有望为卵巢癌靶向治疗提供参考。Objective To investigate the mechanism of combined targeted inhibition of fibroblast growth factor receptor(FGFR)and mammalian target of rapamycin(mTOR)in the occurrence and development of ovarian cancer.Method Eighty female SD rats were collected.Sixty of them were used to establish rat model of ovarian cancer and were randomly divided into experimental group 1(injected with FGFR inhibitor,20),experimental group 2(injected with mTOR inhibitor,20)and combined group(injected with mTOR inhibitor and FGFR inhibitors,20).The remaining 20 rats were included in routine group(fed routinely and injected with normal saline).The relative mRNA and protein expression levels of tumor microenvironment-related factors[extracellular signalregulated kinase(ERK),protein kinase R-like endoplasmic reticulum kinase(pERK),hypoxia-inducible factor-1α(HIF-1α)]in different groups were compared.Then,the tissue fluid obtained after sacrifice of the model rats was co-cultured with macrophages.The cell proliferation rates and apoptosis rates of experimental group 1,experimental group 2 and combined group were observed.Result The relative mRNA expression levels and protein expression levels of ERK,pERK and HIF-1α in combined group and routine group were significantly lower than those in experimental group 1 and experimental group 2(all P<0.05),but there were no significant differences in the above indexes between combined group and routine group(all P>0.05).After intervention,the proliferation rate of ovarian cancer cells was as follows:combined group<experimental group 2<experimental group 1(all P<0.05);the apoptosis rate of ovarian cancer cells was as follows:combined group>experimental group 2>experimental group 1(all P<0.05).Conclusion Comb ined targeted inhibition of FGFR and mTOR can significantly reduce the proliferation of ovarian cancer and effectively promote the apoptosis of cancer cells,which is expected to provide reference for targeted therapy of ovarian cancer.

关 键 词：卵巢癌 成纤维细胞生长因子受体 哺乳动物雷帕霉素靶蛋白 靶向抑制 机制 

分 类 号：R737.31[医药卫生—肿瘤]