乙酰肝素酶抑制剂OGT2115通过Wnt/β-catenin信号通路促进胆囊癌细胞的凋亡  

Heparanase inhibitor OGT2115 promotes apoptosis in gallbladder carcinoma cells through the Wnt/β-catenin signaling pathway

作　　者：陈佳伟 常卫才 刘子祥 王郑林 周少波[1] CHEN Jiawei;CHANG Weicai;LIU Zixiang;WANG Zhenglin;ZHOU Shaobo(The Second Affiliated Hospital of Bengbu Medical College,Bengbu 233000,China;Anhui Province Key Laboratory of Tissue Transplantation,Bengbu 233000,China;不详)

机构地区：[1]蚌埠医学院第二附属医院普外科,安徽蚌埠233000 [2]安徽省组织移植重点实验室,安徽蚌埠233000

出　　处：《实用医学杂志》2022年第19期2414-2418,共5页The Journal of Practical Medicine

基　　金：安徽省卫生健康委科研项目(编号:AHWJ2021a012);安徽省高等学校自然科学研究项目(编号:KJ2020A0564);蚌埠医学院自然科学重点项目(编号:2021byzd197)。

摘　　要：目的探讨乙酰肝素酶抑制剂OGT2115、Wnt/β-catenin信号通路在对胆囊癌细胞生物学功能的影响。方法用不同浓度梯度的HPSE抑制剂OGT2115作用于胆囊癌细胞GBC-SD,CCK-8法检测OGT2115对GBC-SD细胞的抑制率,流式细胞术检测GBC-SD的凋亡比例,ELISA检测OGT2115对细胞上清液HPSE,Fas以及β-catenin活性,将实验分为对照组、OGT2115组和IWR-1+OGT2115组,qRT-PCR和Western blot检测OGT2115对细胞凋亡基因(Caspase-3、Bax、Bcl-2)和Wnt/β-catenin信号通路相关基因(β-catenin、c-MYC、CyclinD1、E-cadherin)表达的影响。结果OGT2115可以抑制GBC-SD增殖,且具有浓度依赖性。OGT2115抑制乙酰肝素酶活性,促进细胞凋亡。qRT-PCR和Western blot结果显示,OGT2115促进caspase-3、cleaved-caspase-3、Bax基因表达水平,而Bcl-2、信号通路相关基因β-catenin、c-MYC、Cyclin D1、E-cadherin表达水平下降,且IWR-1抑制该信号通路后,OGT2115对凋亡及信号通路的作用更加明显。结论乙酰肝素酶抑制剂OGT2115抑制GBC-SD细胞的生长与活性,可能通过Wnt/β-catenin通路促进凋亡。Objective To investigate the effect of acetyl heparanase inhibitor OGT2115 and Wnt/β-catenin signaling pathway on the biological function of gallbladder carcinoma cells.Methods GBC-SD cells were treated with different gradients of HPSE inhibitor OGT2115,the inhibition of GBC-SD cells was detected by CCK-8 assay,and the apoptotic ratio of GBC-SD cells was detected by flow cytometry.The detection of OGT2115 on HPSE,Fas andβ-catenin activities in cell supernatants was performed by ELISA.The experiment was divided into control group,OGT2115 group and IWR-1+OGT2115 group,the effects of OGT2115 on the expression of apoptotic genes(Caspase-3,Bax,Bcl-2)and Wnt/β-catenin signaling pathway-related genes(β-catenin,c-MYC,CyclinD1,E-cadherin)by qRT-PCR and Western blot.Results OGT2115 inhibited the proliferation of GBC-SD in a concen-tration-dependent manner.OGT2115 inhibited acetyl heparanase activity and promoted apoptosis.The qRT-PCR and Western-Blot results showed that OGT2115 promoted the expression levels of caspase-3,cleaved-caspase-3,and Bax genes,while the expression levels of Bcl-2,signaling pathway-related genesβ-catenin,c-MYC,Cyclin D1,and E-cadherin decreased,and the effect of OGT2115 on apoptosis and signaling pathway was more obvious after IWR-1 inhibited this signaling pathway.Conclusions The acetyl heparinase inhibitor OGT2115 inhibited the growth and activity of GBC-SD cells and may promote apoptosis through the Wnt/β-catenin signaling pathway.

关 键 词：胆囊癌 乙酰肝素酶 肝素酶抑制剂 细胞凋亡 信号通路 

分 类 号：R735.8[医药卫生—肿瘤] Q279[医药卫生—临床医学]