靶向四次跨膜L6家族成员1通路抑制三阴性乳腺癌干细胞自我更新的研究  

Targeting Transmembrane 4 L6 Family Member 1 Pathway in the Inhibition of Self-Renewal of Triple Negative Breast Cancer Stem Cells

作　　者：张伟杰[1] 薛磊[1] 马志俊[1] 李冬荟 王留兴[1] ZHANG Weijie;XUE Lei;MA Zhijun;LI Donghui;WANG Liuxing(Department of Oncology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院肿瘤科,河南郑州450052

出　　处：《肿瘤基础与临床》2019年第6期461-465,共5页journal of basic and clinical oncology

基　　金：河南省高等学校重点科研项目(17A320057);河南省科技攻关计划项目(192102310114)。

摘　　要：目的研究四次跨膜L6家族成员1 (TM4SF1)在三阴性乳腺癌干细胞中的作用及靶向抑制TM4SF1通路对三阴性乳腺癌干细胞自我更新的影响。方法构建TM4SF1-RNA干扰质粒,转染三阴性乳腺癌MDA-MB-231细胞系,经流式细胞仪进行分选,观察乳腺癌干细胞比例,进而进行细胞生长曲线、乳腺癌干细胞的克隆形成以及裸鼠成瘤能力实验等功能检测。结果特异性转染TM4SF1-RNA干扰质粒后,TM4SF1表达显著被抑制,乳腺癌干细胞比例降低,但细胞增殖速度无明显差异;形成的克隆数目明显降低。接种5周后三阴性乳腺癌MDA-MB-231细胞系组瘤体体积明显大于三阴性乳腺癌MDA-MB-231细胞系DsiRNA-1组。结论通过靶向TM4SF1通路能够抑制三阴性乳腺癌干细胞自我更新,该通路有可能作为乳腺癌干细胞新的治疗靶点,对三阴性乳腺癌具有潜在的治疗价值。Objective To study the role of transmembrane 4 L6 family member 1( TM4 SF1) in the triple negative breast cancer stem cells and the effect of targeted inhibition of TM4 SF1 pathway on the self-renewal of triple-negative breast cancer stem cells. Methods The TM4 SF1-RNA interference plasmid was constructed,and were transfected to triple negative breast cancer cell line MDA-MB-231,and then were sorted by flow cytometry to observe the proportion of breast cancer stem cells. Then,cell growth curves,breast cancer stem cell clone formation,and tumorigenicity of nude mice were done. Results After specific transfection of TM4 SF1-RNA interference plasmid,TM4 SF1 expression was significantly inhibited,and at the same time,the proportion of breast cancer stem cells were reduced,but the cell proliferation rate was not significantly different in each group;the number of colonies formed were significantly reduced. In 5 weeks after inoculation,the tumor volume of the MDA-MB-231 cell line group was significantly larger than that of the MDA-MB-231 cell line DsiRNA-1 cell line group. Conclusion Targeting TM4 SF1 pathway can inhibit the self-renewal of breast cancer stem cells,this pathway may be a new therapeutic target for breast cancer stem cells,and has potential therapeutic value for triple negative breast cancer.

关 键 词：四次跨膜L6家族成员1 三阴性乳腺癌 干细胞 

分 类 号：R737.9[医药卫生—肿瘤]