沉默Nanog联合SNX-2112对人食管癌干细胞样细胞的抑制作用  

Combiantion of silence of Nanog with SNX-2112 inhibited the proliferation of esophageal cancer stem-like cells

作　　者：徐单单 王霞[1] 黄慧清[1] 陈素红[1,2] XU Dandan;WANG Xia;HUANG Huiqing;CHEN Suhong(Guangdong Food and Drug Vocational College,Guangdong Guangzhou 510520,China;College of Life Science and Technology,Jinan University,Guangdong Guangzhou 510632,China.)

机构地区：[1]广东食品药品职业学院,广东广州510520 [2]暨南大学生命科学技术学院,广东广州510632

出　　处：《现代肿瘤医学》2020年第23期4021-4027,共7页Journal of Modern Oncology

基　　金：国家自然科学基金青年基金(编号:81702990);广东医学科研基金(编号:A2017312&A2018540);广东食品药品职业学院校级课题(编号:2016YZ023)。

摘　　要：目的:通过沉默Nanog探讨其对Hsp90抑制剂SNX-2112诱导食管癌干细胞样细胞的裸鼠移植瘤抑制效果。方法:CCK-8分析细胞受到药物作用活性,Ki-67检测细胞增殖情况,Western blotting检测凋亡蛋白Bcl2、Bax、Bcl-xL表达情况。建立BALB/c裸鼠移植瘤模型,裸鼠分为四组,包括DMSO组、shNanog组、SNX-2112组、shNanog与SNX-2112联合用药组,每组3只。隔天给药,总共给药7次,脱颈处死小鼠,测量小鼠体重,瘤组织经HE染色,免疫组化分析Caspase3的表达情况与Hsp90客户蛋白pErk表达情况。结果:联合用药组细胞活性显著受到抑制(P<0.05),Ki-67实验显示联合用药组细胞增殖受到抑制(P<0.05),Bcl2与Bcl-xL蛋白表达下调(P<0.05),Bax表达水平上调(P<0.05)。联合用药组小鼠瘤重明显低于SNX-2112组以及shNanog组(P<0.05),HE染色结果显示沉默Nanog与SNX-2112联合用药显著性诱导肿瘤细胞凋亡,免疫组化研究显示Caspase3在两者联合用药组表达水平较高(P<0.05),Hsp90客户蛋白pErk表达有下调的趋势(P<0.05)。结论:沉默Nanog有助于提高SNX-2112诱导食管癌干细胞样细胞的裸鼠移植瘤细胞凋亡作用。Objective:To explore the effects of SNX-2112 combination with silencing Nanog on the apoptosis of esophageal cancer stem-like cells(ECSLCs).Methods:CCK8 assay and Ki-67 assay were employed to evaluate the inhibitory effect of shNanog and SNX-2112 on the viability and proliferation of ECSLCs.Western blotting was used to study the expression level of apoptosis proteins.Establishing xenograft tumor model,mice were divided randomly into four groups,including DMSO group,shNanog group,SNX-2112 group and combining group.Every group contained three mice and the mice were intraperitoneally injected SNX-2112 every other day.After 15 days,the mice were scarified by cervical dislocation and the body weight of the mice was measured.The tumor was harvested.The tumor was evaluated by HE staining and the level of the Caspase3 and pErk were analyzed.Results:The viability of ECSLCs was inhibited significantly in combination treatment group(P<0.05).The proliferation of ECSLCs was suppressed(P<0.05).The levels of Bcl2,Bcl-xL and Bax were changed in combination treatment group(P<0.05).The tumor weight in the mice was smaller significantly in combination treatment group than SNX-2112 and shNanog alone group.The HE staining results demonstrated that SNX-2112 combined with shNanog significantly induced apoptosis of the esophageal cancer stem-like cells.Immunohistochemistry(IHC) results showed that the level of the Caspase3 was increased and the client protein pErk was decreased(P<0.05).Conclusion:SNX-2112 combined with shNanog synergistically suppressed the proliferation of the esophageal cancer stem-like cells.

关 键 词：沉默Nanog HSP90 SNX-2112 食管癌干细胞样细胞 裸鼠移植瘤 

分 类 号：R735.1[医药卫生—肿瘤]