雷公藤红素通过下调FAT10抑制结直肠癌细胞增殖促进凋亡的研究  

Celastrol inhibits proliferation and promotes apoptosis of colorectal cancer cells by downregulating FAT10

作　　者：王雪丽 张昱 郝荣荣 胡英男 王建伟[1] 张威 Wang Xueli

机构地区：[1]浙江工业大学药学院,310032 [2]浙江省人民医院,310014 [3]浙江中医药大学第二临床医学院,310053 [4]浙江中医药大学附属第二医院,310005

出　　处：《浙江临床医学》2023年第8期1113-1116,共4页Zhejiang Clinical Medical Journal

基　　金：国家自然科学基金资助项目(82274475);浙江省中医药科技计划项目(2022ZA016);浙江省大学生科技创新活动计划(新苗人才计划)资助项目(2022R410B048);浙江中医药大学2022年浙江省教育厅一般科研项目(Y202248721)。

摘　　要：目的探究人白细胞抗原F位点相邻转录本10(FAT10)在雷公藤红素(Cel)诱导结直肠癌(CRC)细胞凋亡过程中的机制。方法体外培养结CRC细胞系SW480和HCT116,CCK-8法检测Cel(0、0.3125、0.625、1.25、2.5、5、10、20μmol/Lol/L)作用24 h后的细胞活力,并计算半数抑制浓度(IC50)。流式细胞仪检测Cel(0、1.25、5μmol/L)作用结CRC细胞的凋亡情况。RT-qPCR和Western blot检测Cel对结CRC细胞中FAT10表达的影响。结果FAT10 mRNA在结CRC细胞系中呈高表达(P<0.01)。Cel显著降低结CRC细胞的增殖(P<0.01),半数抑制浓度分别为SW480:3.03μmol/L;HCT116:1.63μmol/L。Cel处理24 h后流式检测FITC+PI+凋亡细胞占比增加(P<0.01)。细胞经Cel刺激后FAT10 mRNA和蛋白的表达水平均有所下降,并且呈剂量依赖性(P<0.05)。结论Cel能明显降低结CRC细胞增殖,促进细胞凋亡并伴随着FAT10的下调。Objective To analyze the mechanism of human leukocyte antigen F site adjacent transcript 10(FAT10)in the induction of apoptosis in colorectal cancer cells by Celastrol(Cel).Methods In vitro culture of colorectal cancer cell lines SW480 and HCT116,the cell viability of Cel(0,0.3125,0.625,1.25,2.5,5,10,20μmol/L)for 24 h was detected by CCK-8 method,and the half inhibitory concentration(IC50)was calculated.The apoptosis of colorectal cancer cells treated by Cel(0,1.25,5μmol/L)was detected by flow cytometry.RT-qPCR and Western blot were used to detect the effect of Cel on the expression of FAT10 in colorectal cancer cells.Results FAT10 mRNA was highly expressed in colorectal cancer cell lines,with statistical significance(P<0.01).Cel significantly decreased the proliferation of colorectal cancer cells(P<0.01),and the median inhibitory concentrations were SW480:3.03μmol/L and HCT116:1.63μmol/L,respectively.The proportion of FITC+PI+apoptotic cells increased by flow cytometry after Cel treatment for 24 h,with statistical significance(P<0.01).FAT10 mRNA and protein expression decreased in dose-dependent manner after Cel treatment,with statistical significance(P<0.05).Conclusion Cel can significantly reduce the proliferation of colorectal cancer cells,promote apoptosis and reduce FAT10.

关 键 词：雷公藤红素 FAT10结直肠癌 凋亡 

分 类 号：R735.34[医药卫生—肿瘤]