Yin Yongjian, Chen Shiyou, Luo Chunli, et al. Research of interferon α2b inhibiting the growth of renal carcinoma by reducing MDSCs in mice. [J]. Journal of Chongqing Medical University 42(5):473-480(2017)
DOI:
Yin Yongjian, Chen Shiyou, Luo Chunli, et al. Research of interferon α2b inhibiting the growth of renal carcinoma by reducing MDSCs in mice. [J]. Journal of Chongqing Medical University 42(5):473-480(2017) DOI: 10.13406/j.cnki.cyxb.001301.
Research of interferon α2b inhibiting the growth of renal carcinoma by reducing MDSCs in mice
Objective:to investigate the effect of interferon α2b on the growth of renal carcinoma in mice
and to explore the potential mechanism. Methods:Renal carcinoma xenograft model was established. After intervention of interferon
transplanted renal carcinoma model was divided into control group and interferon α2b group. The volume and weight of transplanted tumor in mice was monitored
and tumor was removed was for HE staining. BCL-2 expression was detected in transplanted tumor by immunohistochemical method.Exosomes from renca cells were separated and purified by ultrafiltration and sucrose gradient centrifugation. The morphology and quantitative of exosomes was identified by transmission electron microscope. The proportion of MDSCs in bone marrow and spleen CD4/CD8 T lymphocytes of mice was determined by flow cytometry. BALB/c mouse model was established and was divided into normal saline group
exosomes group and renca cell group. On 10
20
30 days after modeling
the MDSCs ratio of bone marrow in each group was detected by flow cytometry. Results:The tumor model of renal carcinoma and experimental model of BALB/c mice were successfully established. Compared with those of control model
the volume and weight of the transplanted tumor treated with interferon α2b were significantly inhibited(P <0.01). HE staining showed that the tumor cells varied in size and morphology
arranged in disorder and had increased nucleus
nucleo cytoplasmic ratio arrhythmia
hyperchromatic nuclei
and abnormal nuclear fission. Immunohistochemistry showed that there was no significant difference in the expression of Bcl-2 protein between the two groups(P>0.05). The exosome was separated and purified. There was no significant difference between the two groups in exosomes(P>0.05). And the interferon α2b could significantly reduce the amount of exosomes secreted by Renca cells compared with that of control group(P=0.000). Compared with that of control group
the proportion of MDSCs in interferon α2b group was significantly decreased(P=0.00)
and the proportion of CD4/CD8 T lymphocytes in tumor bearing mice was significantly increased(P=0.000). In the BALB/c mice model experiment
on 10 days
20 days and 30 days
MDSCs of exosomes group and Renca group were significantly higher than those of normal saline group(P<0.01). There was no significant difference in MDSCs between exosomes group and Renca cells group on 10 days
20 days and 30 days(P>0.05). In each exosomes group and Renca cell group
the proportion of MDSCs on 20 days and 30 days was significantly increased than that on 10 days
with statistical significances(P < 0. 05)
and there was no significant change in the proportion of MDSCs between 20 days and30 days(P>0.05). There was no significant difference in the proportion of MDSCs in saline group on 10
20
and 30 days(P>0.05).Conclusion:Interferon α2b inhibits the secretion of exosome from renca cells
and exosomes from renca cell are involved in the activation and proliferation of mouse MDSCs in vivo
resulting in the restriction of activation and proliferation of MDSCs