Effect of folic-acid modified liposome quercetin on the immune function of triple-negative breast cancer bearing mice
Objective To investigate the anti-tumor and immunomodulatory effects of folic acid-modified liposome quercetin(FLQ)on triple-negative breast cancer(TNBC)orthotopic transplantation model mouse.Methods A total of 60 5-week-old BALB/c female mice were selected from Hubei Bainte Biotechnology Co.,L.They were randomly divided into control group,model group and FLQ group(50 mg/kg),with 20 mice in each group by random number method to establish orthotopic TNBC model.Corresponding drugs were given to intervene for 2 weeks,survival state of mice was observed and tumor size were measured every three days.The mice were killed 24 h after the last administration,the spleen and thymus mass were measured,and spleen and thymus indexes were calculated.Serum interleukin(IL)-2,tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),IL-4,IL-10 and transforming growth factor-β(TGF-β)were detected by enzyme linked immunosorbent assay(ELISA).Flow cytometry was used to de-tected the proportion of T lymphocytes in peripheral blood.Cell counting kit-8(CCK-8)and clonal forma-tion assays were used to detect proliferation of MDA-MB-231 cells.Data were analyzed using student's t-test for two groups.Results Compared with model group,the tumor growth trend in FLQ group was slowed down,and tumor size was reduced(P＜0.05).Spleen and thyroid index in FLQ group was higher than that in model group(6.72±0.57 vs.3.25±0.31,t=12.923,P＜0.05;2.08±0.23 vs.1.34± 0.12,t=5.569,P＜0.05).The levels of IL-2,TNF-α and IFN-γ in serum in FLQ group were higher than those in model group[(221.37±10.51)vs.(136.45±8.72)pg/ml,t=6.726,P＜0.05;(75.24±5.18)vs.(48.32±4.37)pg/ml,t=6.875,P＜0.05;(293.55±11.83)vs.(204.39± 13.04)pg/ml,t=8.042,P＜0.05].The serum levels of IL-4,IL-10 and TGF-β in FLQ group were lower than those in model group[(118.29±6.22)vs.(167.12±8.35)pg/ml,t=4.350,P＜0.05;(205.64±18.59)vs.(273.48±17.62)pg/ml,t=4.505,P＜0.05;(193.45±9.42)vs.(252.46± 12.58)pg/ml,t=3.550,P＜0.05].The number of CD4+T lymphocytes in peripheral blood of FLQ group was greater than that of model group[(48.53±4.86)％vs.(35.26±2.41)％,t=5.127,P＜0.05].The number of CD8+T lymphocytes in peripheral blood of FLQ group was less than that of model group[(10.14±2.03)％vs.(17.45±1.78)％,t=3.938,P＜0.05].TheCD4+/CD8+ratio in pe-ripheral blood of FLQ group was higher than that of model group(4.12±0.27 vs.2.34±0.15,t=5.099,P＜0.05).Compared with control group,the number of MDA-MB-231 cell clones was reduced[(38.52±2.54)％vs.(78.29±4.01)％,t=9.900,P＜0.05]and cell viability was inhibited over the time in FLQ group(P＜0.05).Conclusion FLQ can significantly inhibit tumor growth and remodel tumor immune microenvironment.
Oldenlandia diffusaFolic acid-modified liposome quercetinTriple-negative breast cancerImmune function
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