| 过表达miR-145的脐带间充质干细胞外泌体改善肾细胞癌细胞786-0对舒尼替尼的药物敏感性 |
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| 引用本文： | 刘强,王玉杰,李前进,拜合提亚·阿扎提. 过表达miR-145的脐带间充质干细胞外泌体改善肾细胞癌细胞786-0对舒尼替尼的药物敏感性[J]. 现代肿瘤医学, 2022, 0(6): 959-966. DOI: 10.3969/j.issn.1672-4992.2022.06.003 |
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| 作者姓名： | 刘强 王玉杰 李前进 拜合提亚·阿扎提 |
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| 作者单位： | 新疆医科大学第一附属医院泌尿外科，新疆 乌鲁木齐 830054 |
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| 基金项目： | 吴阶平医学基金会临床科研专项资助基金(编号:320.6750.19094-43)。 |
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| 摘 要： | 目的:探究过表达miR-145的脐带间充质干细胞外泌体对肾透明细胞癌细胞786-0舒尼替尼药物敏感性的影响.方法:分离纯化人脐带间充质干细胞(human umbilical cord mesenchymal stem cells,hUCMSCs),流式细胞术鉴定其细胞表型,茜素红及红油O染色观察其成骨与成脂分化能力;差...
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| 关 键 词： | 肾细胞癌 脐带间充质干细胞 外泌体 miR-145 舒尼替尼 化疗敏感性 |
Effects of exosomes derived from overexpressing miR-145 umbilical cord mesenchymal stem cells improved the drug sensitivity of 786-0 renal cell carcinoma cells to sunitinib |
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| LIU Qiang,WANG Yujie,LI Qianjin,Baihetiya·Azhati. Effects of exosomes derived from overexpressing miR-145 umbilical cord mesenchymal stem cells improved the drug sensitivity of 786-0 renal cell carcinoma cells to sunitinib[J]. Journal of Modern Oncology, 2022, 0(6): 959-966. DOI: 10.3969/j.issn.1672-4992.2022.06.003 |
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| Authors: | LIU Qiang WANG Yujie LI Qianjin Baihetiya·Azhati |
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| Affiliation: | Department of Urology,the First Affiliated Hospital of Xinjiang Medical University,Xinjiang Urumqi 830054，China. |
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| Abstract: | Objective:To investigate the effect of umbilical cord mesenchymal stem cell exosomes with overexpression of miR-145 on the drug sensitivity of renal clear cell carcinoma 786-0 to sunitinib.Methods:Human umbilical cord mesenchymal stem cells(hUCMSCs)were isolated and purified,and their phenotypes were identified by flow cytometry.Exosomes of hUCMSCs(hUCMSCs-Exo)were isolated by differential and hypervelocity centrifugation.The morphology of hUCMSCs-Exo was observed by electron microscope.The size and distribution of hUCMSCs-Exo were detected by particle size analysis(NTA).The expressions of CD9,CD63 and CD81 were detected by Western blot.The expression of miR-145 in hUCMSCs and hUCMSCs-Exo was detected by RT-PCR.CCK-8 assay was used to detect the proliferation activity and half inhibitory concentration(IC50)changes of 786-0 cells treated with different concentrations of hUCMSCs-Exo(50,100,200μg/mL).Annexin V-FITC/PI double staining combined with flow cytometry was used to detect the pro apoptotic effect of sunitinib on 786-0 cells treated with different concentrations of hUCMSCs-Exo.BALB/c nude mice were used to verify the effect of hUCMSCs-Exo overexpressing miR-145 on sunitinib inhibiting the growth of renal clear cell carcinoma.Results:hUCMSCs with stem cell phenotype and osteogenic and adipogenic differentiation potential were successfully isolated,and the diameter of hUCMSCs-Exo was about 30~130 nm,with high expression of CD9,CD63 and CD81.PKH67 labeling results showed that hUCMSCs-Exo could be successfully ingested and engulfed by 786-0 cells,recombinant adenovirus infection could significantly increase the expression level of miR-145 in hUCMSCs and hUCMSCs-Exo,and hUCMSCs-Exo overexpressing miR-145 could significantly promote the proliferation inhibition rate of sunitinib on 786-0 cells in a concentration dependent manner,reduce its IC50value,and increase the apoptosis rate of 786-0 cells.In vivo experiments also showed that hUCMSCs-Exo overexpressing miR-145 could increase the drug sensitivity of 786-0 cells to sunitinib and the growth inhibition of renal cell carcinoma.Conclusion:hUCMSCs can effectively transfer the overexpressed miR-145 into the exosome and be absorbed by RCC cells,thus improving the drug sensitivity of RCC to sunitinib in vitro and in vivo. |
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| Keywords: | renal cell carcinoma umbilical cord mesenchymal stem cells exosomes miR-145 sunitinib drug sensitivity |
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