|Table of Contents|

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

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2022 06
Page:
959-966
Research Field:
Publishing date:

Info

Title:
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
Author(s):
LIU Qiang; WANG Yujie; LI Qianjin; Baihetiya·Azhati
Department of Urology,the First Affiliated Hospital of Xinjiang Medical University,Xinjiang Urumqi 830054，China.
Keywords:
renal cell carcinoma; umbilical cord mesenchymal stem cells; exosomes; miR-145; sunitinib; drug sensitivity
PACS:
R737.11
DOI:
10.3969/j.issn.1672-4992.2022.06.003
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（50,100,200 μg/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 IC50 value,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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Memo

Memo:
吴阶平医学基金会临床科研专项资助基金（编号：320.6750.19094-43）
Last Update: 1900-01-01