Immunoregulatory effect of gemcitabine on ovarian cancer xenograft-bearing mice
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Abstract:
Objective:To observe the interfering and regulating effect of gemcitabine (GEM) on the immune mi-croenvironment of ovarian tumor bearing mice. Methods: C57BL/6 mice were inoculated subcutaneousely with ID8 cells to construct ovarian cancer xenograft model. The mice in the experimental group were injected with GEM intraperitoneally and the control group was injected with saline. Growth of the tumor was observed. The percentage of the regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in spleen and tumor tissues of the mice were detected by FCM. RT-qPCR was used to detect the mRNA expression of arginase-1 (Arg-1) and Foxp3 in tumor tissues. The ratio of CD8 + T cells in spleen of the mice was detected by FCM. The serum IFN-γ and IL-2 level was detected by ELISA assay. Results: Tumor growth in tumor-bearing mice was significantly inhibited after GEM treatment ([366.8±44.88] vs [499.3±24.14] mm 3 , P<0.01). Tregs ratio in tumor tissues and spleen were significantly lower than controls, respectively ([12.71±2.31]% vs [20.36±2.65]%, [10.09±1.69]% vs [13.79±1.31]%; all P<0.01).The mRNA levels of Foxp3 ([4.30±0.46] vs [6.35±0.58], P<0.01) and Arg-1 ([13.26±0.37] vs [16.32±0.38], P<0.01)in the treatment group were significantly lower than that in the control group. Percentage of the CD8 + T lymphocytes in treatment and control groups had no significant difference ([11.08±1.29]% vs [11.12±1.06]%; P>0.05), but the se-rum level of IFN-γ ([71.90±2.28] vs [53.91±3.91] pg/ml,P<0.01) and IL-2 ([51.46±1.69] vs [40.90±1.50] pg/ml; P<0.01) was significantly increased compared with control group. Conclusion: GEM down-regulated immunosuppres-sive activity and up-regulated anti-cancer immunogenicity of tumor-bearing mice, which might provide the experi-mental basis of GEM serving as immunotherapy intervention for ovarian cancer.