miR-145靶向ADAM17对裸鼠三阴性乳腺癌移植瘤生长的影响及机制

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【中图分类号】R737.9 【文献标志码】A

【AbstractObjective：TinvestigatetheefectofappingtheanalogofmiR-145（agomR-145）totargetdsintegiandmtalopo tease17（ADAM17）onthegrowthof triple-negativebreastcancer（TNBC）xenografttumors innude miceandtheunderlying mechanism. Methods ：A subcutaneous xenograft tumor model was established in nude mice with MDA-MB-231 cells（ n =30）. The 30 nude mice wererandomlydivided intoagomiRgroup，agomiR-NC group，andcontrol group toreceive intratumoral injectionof 100μL of agomiR- ⋅145（0.33g/L ），agomiR-NC（0.33g/L），and normal saline，respectively.Weexamined tumor tissue morphology with HE staining；measuredtheexpreionofiR-145，ADAM17，andepderagrowthfactorreeptoEGFR）inmorsuesbyaltieoly merase chain reaction（RT-PCR）；and determined the protein expression of ADAM17，EGFR，and p -EGFR in tumor tissues by immunohistochemistryandWesterblot.Results：ThetumorgrowthintheagomiRgroupwasslow，withasignificantlysmalertumorolume than those in the control group and the agomiR-NC group（ P<0.05） .The results of HE staining showed more severe necrosis and hemorrhage withintumortisues inthecontrolgroupandtheagomiR-NCgroupthanintheagomiRgroup.RT-PCRresultsshowedthatthe expressionlevel of miR-145intheagomiR group was significantly higher thanthosein theagomiR-NCandcontrol groups（ P<0.001 ）；

theagomiR group had a significantly lower mRNA expression level ofADAM17 thanthe other two groups（ P<0.05 ）;and there was no significantdifferenceinEGFRmRNA expressionbetweenthe three groups（ P>0.05 ）.Immunohistochemistry and Western blot detected significantlylowerproteinexpressionlevelsofADAM17and EGFR intheagomiR group thanin the agomiR-NC group and the control group（ P<0.05） .Conclusion：AgomiR-145 inhibitsthe growth of

TNBC xenografts in nude mice by targeted suppression of ADAM17-EGFR activity. 【Key Words】micro RNA-145;adisintegrinand metalloprotease 17;triple-negative breastcancer;targeted therapy

解聚素-金属蛋白酶17（adisintegrinand metal-loprotease17，ADAM17）是一种存在于细胞膜表面的可剪切活化多种跨膜蛋白及表皮生长因子受体（epidermal growth factor receptor，EGFR）配体的外侧结构域，通过激活EGFR及下游通路，促进肿瘤发生发展[-]。（剩余9770字）