Down regulation of dopamine receptor D2 inhibits the growth of EO771 cell-based xenograft breast tumor through promoting Th1 cell differentiation
10.3781/j.issn.1000-7431.2023.2210-0746-0538
- VernacularTitle:下调多巴胺受体D2表达促进Th1细胞分化可抑制乳腺癌EO771细胞移植瘤的生长
- Author:
Lei ZHU
1
;
Hong YIN
;
Chunyan WU
;
Haowei GUO
;
Ping ZHOU
;
Yuqing WU
Author Information
1. 南京医科大学附属妇产医院乳腺外科,江苏南京 210004
- Keywords:
Diffuse large B-cell lymphoma;
R-CODP regimen;
Rituximab;
Liposomal doxorubicin;
Interstitial pneumonia;
Corticosteroids
- From:
Tumor
2023;43(11):866-875
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role and mechanism of dopamine receptor D2(DRD2)in the immune microenvironment of breast cancer. Methods:The xenograft model of breast cancer is established using female C57BL/6J mice and murine breast cancer EO771 cells.Mice with transplanted tumor were treated by intraperitoneal injection of the specific antagonist of DRD2,thioridazine,while PBS was injected intraperitoneally in the control group.siDRD2 targeting DRD2 gene was intratumorally injected to tumor-bearing mice[negative control siRNA(siNC)was injected to the control group].The percentage of Ki-67 positive cells and CD4+T lymphocytes in tumor tissue was examined by immunohistochemical analysis.The proportion of CD45+CD4+T lymphocytes,CD45+CD4+IFNγ+Th1 cells and CD45+CD4+IL-1 7+Th17 cells was detected by flow cytometry. Results:Compared with the control group,the tumor volume(P＜0.05),tumor mass(P＜0.001)and the proportion of Ki-67 positive cells(P＜0.001)in tumor tissue were decreased in the thioridazine-treated group.The proportion of CD45+immune cells(P＜0.05)and CD4+T lymphocytes(P＜0.001)in thioridazine-treated group was higher than that in the control group.The proportion of Th1 cells(CD45+CD4+IFNγ+)increased(P＜0.001)in thioridazine-treated group.There was no significant changes in the proportion of Th1 7 cells(CD45+CD4+IL-1 7+)(P＞0.05).Compared with the control group(siNC),the tumor volume(P＜0.05),tumor mass(P＜0.001)and the proportion of Ki-67 positive cells(P＜0.001)were decreased in siDRD2 group.The proportion of tumor infiltrating CD4+T lymphocytes(P＜0.001)and Th1 cells(P＜0.001)in the siDRD2 group was higher than that in the siNC group,whereas the change in the proportion of Th1 7 cells was not statistically significant(P＞0.05). Conclusion:Down-regulation of DRD2 could promote the differentiation of Th1 cells and inhibit the proliferation of breast cancer cells in a mouse breast cancer model.
