BMP-4对甲状腺乳头状癌细胞生物学行为的影响及其分子机制  

Effect of BMP-4 on cell biological behaviors in papillary thyroid carcinoma and its molecular mechanism

作　　者：孟晓梅[1] 巴茂文[1] 王绍光[1] 于岁 李宁[1] 唐与晓[1] MENG Xiaomei;BA Maowen;WANG Shaoguang;YU Sui;LI Ning;TANG Yuxiao(The Affiliated Yantai Yuhuangding Hospital of Qingdao University,Yantai 264000,China)

机构地区：[1]青岛大学附属烟台毓璜顶医院,山东烟台264000

出　　处：《山东医药》2021年第2期1-5,共5页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(81701453);山东省医药卫生科技发展计划项目(2018WS030,2017WS843,2016WS0710)。

摘　　要：目的观察骨形态发生蛋白4(BMP-4)对甲状腺乳头状癌(PTC)细胞增殖、凋亡和侵袭能力的影响,并探讨其与Smad1信号通路的关系。方法常规培养PTC细胞系B-CPAP、TPC-1、K1细胞,采用qPCR法检测BMP-4 mRNA表达水平。取BMP-4 mRNA表达量较低的B-CPAP细胞,将其分为阴性对照组和过表达组,分别感染阴性片段、过表达BMP-4重组慢病毒;取BMP-4 mRNA表达量较高的TPC-1细胞,将其分为阴性对照组和干扰组,分别感染无效干扰片段和干扰BMP-4重组慢病毒。采用MTT法检测各组细胞增殖能力,流式细胞仪检测细胞凋亡情况,Corning实验检测细胞侵袭能力,qPCR法及Western blotting法检测E-Cadherin、Vimentin、Smad1 mRNA及蛋白表达。结果B-CPAP细胞过表达组细胞增殖能力较阴性对照组增加(P<0.01),细胞凋亡及侵袭能力无明显变化(P均>0.05),E-Cadherin、Vimentin、Smad1 mRNA及蛋白表达无明显变化(P均>0.05)。TPC-1细胞干扰组细胞增殖能力较阴性对照组下降,细胞凋亡增加,细胞侵袭能力下降,Vimentin蛋白表达降低(P<0.05或<0.01),E-Cadherin、Smad1蛋白表达无明显变化(P均>0.05)。结论BMP-4可促进PTC细胞增殖、抑制其凋亡,增强其侵袭转移能力,其机制与诱导上皮间质转化有关;BMP-4促进PTC侵袭转移不是通过Smad1信号通路发挥作用的。Objective To observe the influence of bone morphogenetic protein 4(BMP-4)on proliferation,apoptosis and invasion of papillary thyroid carcinoma(PTC)cells and to investigate its correlation with Smad1 signaling pathway.Methods BMP-4 mRNA expression was measured by real-time fluorescence quantitative PCR(qPCR)in PTC cell lines B-CPAP,TPC-1,and K1.B-CPAP cells with lower BMP-4 expression were divided into the negative control group and overexpression group,and were transfected with invalid vector and the recombined BMP-4 lentiviral vector,respectively.TPC-1 cells with higher BMP-4 expression were divided into the negative control group and interfered group,and were transfected with invalid vector and BMP-4 interference lentiviral vector,respectively.MTT assay and Corning assay were used to detect cell proliferation and cell invasion,respectively.The expression levels of E-Cadherin,Vimentin and Smad1 were determined by qPCR and Western blotting.Results The proliferation of B-CPAP cells increased in the overexpression group as compared with that of the negative control group(P<0.01);there were no significant changes in the apoptosis,invasive ability,E-Cadherin,Vimentin,or Smad1 mRNA and protein expression levels(all P>0.05).The proliferation of TPC-1 cells was inhibited and the apoptosis increased,the invasive ability decreased and the protein expression of Vimentin decreased significantly in the interfered group as compared with those of the negative control group(P<0.05 or P<0.01);there were no significant changes in the protein expression of E-Cadherin and Smad1(P>0.05).Conclusions BMP-4 can promote cell proliferation,inhibit apoptosis,and enhance invasion and metastasis in PTC cells,and its mechanism of action is related to the induction of EMT.The influence of BMP-4 on cell invasion and metastasis was independent of Smad1 signaling pathway.

关 键 词：甲状腺乳头状癌 骨形态发生蛋白4 上皮间质转化 细胞增殖 细胞凋亡 细胞侵袭 Smad1蛋白 

分 类 号：R736.1[医药卫生—肿瘤]