MSC-exo一种新型细胞递送工具转运靶向基因调控胰腺癌增殖效应分析OACSTPCD
Effect of MSC-exo,a New Cell Delivery Tool,on Gene Delivery and Proliferation of Pancreatic Cancer
目的 观察 1 种新型细胞递送工具(MSC-exo)转运靶向基因调控胰腺癌增殖效应.方法 透射电子显微镜(transmission electron microscope,TEM)和纳米颗粒跟踪分析技术(nanoparticle tracking analysis,NTA)鉴定人间充质干细胞外泌体(human mesenchymal stem cell exosomes,MSC-exo)并转运miR-450a-5p进入CFPAC-1,探讨miR-450a-5p靶向BZW2 抑制胰腺癌细胞增殖效应.基因技术处理Pc-BZW2,CCK-8、EdU、细胞划痕、Transwell验证MSC-exo与MSC-exo-miR-450a-5p对细胞的抑制作用.结果 与胰腺正常组织相比miR-450a-5p在胰腺癌组织中低表达(P<0.05),CFPAC-1 细胞MSC-exo-miR-450a-5p外泌体标记蛋白CD63、TSG101 表达高于MSC-exo(P<0.05).CCK-8、EdU、细胞划痕、Transwell实验显示MSC-exo-miR-450a-5p较MSC-exo可显著抑制CFPAC-1 细胞增殖、侵袭和迁移(P<0.05).通过双荧光素酶实验证实,miR-450a-5p靶向BZW2,并且RT-qPCR和免疫印迹检测miR-450a-5p和 BZW2 表达成负性相关(P<0.05).过表达BZW2,CCK-8、EdU、细胞划痕、Transwell实验均证实,pc-BZW2 逆转MSC-exo-miR-450a-5p对CFPAC-1 的抑癌功能,免疫印迹检测PCNA、Ki-67、MMP2、MMP9,结果与上述实验一致(P<0.05).结论 hMSC-exo是 1 种新的递送系统,靶向BZW2 转运miR-450a-5p抑制胰腺癌细胞的生物学恶性,为胰腺癌靶向治疗研究提供了重要线索.
Objective To observe the effect of a new cell delivery tool(MSC exo)on the proliferation of pancreatic cancer by transferring targeted genes.Methods Transmission Electron Microscope(TEM)and Nanoparticle Tracking Analysis(NTA)were used to identify human mesenchymal stem cell exosomes(MSC-exo)and transport miR-450a-5p into CFPAC-1,to explore the effect of miR-450a-5p targeting BZW2 on inhibiting the proliferation of pancreatic cancer cells.Results The expression of miR-450a-5p was low in pancreatic cancer tissue(P<0.05),and the expression of CD63 and TSG101 of MSC-exo-miR-450a-5p in CFPAC-1 cells was higher than that of MSC-exo by Western blot(P<0.05).CCK-8 and EdU results showed that MSC-exo-miR-450a-5p significantly inhibited the proliferation of CFPAC-1 cells(P<0.05).Cell scratch and Transwell experiments showed that MSC-exo-miR-450a-5p can inhibit the migration and invasion of CFPAC-1 cells(P<0.05).Through dual luciferase assay,it was confirmed that miR-450a-5p targets BZW2,and RT-qPCR and Western blotting showed a negative correlation(P<0.05)between miR-450a-5p and BZW2 expression.Overexpression of BZW2,CCK-8,EdU,cell scratch,and Transwell experiments confirmed that pc-BZW2 reversed the anti-cancer function of MSC-exo-miR-450a-5p on CFPAC-1.Western blot detected PCNA,Ki-67,MMP2,MMP9,and the results were consistent with the above experiments(P<0.05).Conclusion hMSC exo is a new delivery system,targeting BZW2 to transport miR-450a-5p to inhibit the biological malignancy of pancreatic cancer cells,which provides an important clue for the research of targeted treatment of pancreatic cancer.
朱磊;李瑞雪;鲍长磊;黄晨宸;梁书鑫;赵振林;朱洪
深圳瑞普逊干细胞与再生医学研究院,广州 深圳 518038
临床医学
胰腺癌间充质干细胞外泌体miR-450a-5pBZW2
Pancreatic adenocarcinomaMesenchymal stem cellExosomesmiR-450a-5pBZW2
《昆明医科大学学报》 2024 (002)
39-48 / 10
深圳市科技创新基础研究基金资助项目(JCYJ20190807103605679)
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