山柰酚调控Wnt/β-catenin途径对前列腺癌小鼠T细胞的影响及作用机制  

Effects and mechanism of Kaempferol on T cell of prostate cancer mice by regulating Wnt/β-catenin pathway

作　　者：瞿小祥 孔东波 鲁小红 江波涛 邹伟 查文良 QU Xiaoxiang;KONG Dongbo;LU Xiaohong;JIANG Botao;ZOU Wei;ZHA Wenliang(Department of Urology,Xianning Central Hospital,Xianning 437100,China)

机构地区：[1]咸宁市中心医院泌尿外科,咸宁437100

出　　处：《中国免疫学杂志》2022年第16期1946-1951,共6页Chinese Journal of Immunology

摘　　要：目的:探究山柰酚调控Wnt/β-catenin途径对前列腺癌小鼠T细胞的影响及作用机制。方法:皮下注射人去势抵抗性前列腺癌细胞系PC3构建前列腺癌小鼠模型。将30只模型小鼠随机分为对照组、山柰酚低剂量组和山柰酚高剂量组(n=10)。山柰酚灌胃干预,剂量分别为15 mg/kg和30 mg/kg,检测肿瘤生长情况。Western blot检测增殖和转移相关蛋白Cyclin D1、Ki67、MMP2和MMP9表达,TUNEL染色检测细胞凋亡。比较各组Wnt/β-catenin通路的转录和翻译水平。流式细胞术和ELISA检测各组CD4^(+)、CD8^(+)、IFN-γ和IL-2水平。结果:三组小鼠各项指标比较差异有统计学意义(P<0.05)。山柰酚低剂量组和山柰酚高剂量组的肿瘤体积、质量、Cyclin D1、Ki67、MMP2、MMP9、Wnt3a、β-catenin mRNA和蛋白水平均显著低于对照组,凋亡指数均显著高于对照组(P<0.05)。且山柰酚高剂量组的肿瘤体积[(180.56±21.56)mm3]、质量[(0.21±0.03)g]、Cyclin D1、Ki67、MMP2、MMP9、Wnt3a、β-catenin mRNA和蛋白水平均显著低于山柰酚低剂量组,凋亡指数[(17.43±1.89)%]显著高于山柰酚低剂量组[(10.05±1.05)%](P<0.05)。三组小鼠的CD4^(+)、CD4^(+)/CD8^(+)、IFN-γ和IL-2水平比较差异有统计学意义(P<0.05)。山柰酚低剂量组和高剂量组中CD4^(+)、CD4^(+)/CD8^(+)、IFN-γ、IL-2水平均显著高于对照组(P<0.05)。山柰酚高剂量组中CD4^(+)[(23.81±1.36)%]、CD4^(+)/CD8^(+)(1.51±0.13)、IFN-γ[(9.15±1.12)ng/ml]和IL-2[(1.78±0.11)ng/ml]水平均显著高于山柰酚低剂量组[(19.45±1.24)%、1.20±0.11、(7.23±0.87)ng/ml,(1.40±0.09)ng/ml,P<0.05]。结论:山柰酚可能通过调控Wnt/β-catenin途径抑制前列腺癌小鼠模型的肿瘤生长和转移,并缓解免疫抑制状态。Objective:To explore the effect of Kaempferol regulation of Wnt/β-catenin pathway on T cells in mice with prostate cancer and its mechanism.Methods:Mice model of prostate cancer was constructed by subcutaneous injection of human castration resistant prostate cancer cell line PC3. Thirty model mice were randomly divided into control group,Kaempferol low-dose group and Kaempferol high-dose group(n=10). Kaempferol was administered by intragastric administration,and the doses were 15 mg/kg and30 mg/kg,tumor growth was measured. Expressions of proliferation and metastasis-related proteins Cyclin D1,Ki67,MMP2 and MMP9 were detected by Western blot,and cell apoptosis was detected by TUNEL staining. Transcription and translation levels of Wnt/β-catenin pathway in each group were compared. Levels of CD4^(+),CD8^(+),IFN-γ and IL-2 in each group were detected by flow cytometry and ELISA.Results:Indicators of three groups of mice had significant differences(P<0.05). Tumor volume,mass,Cyclin D1,Ki67,MMP2,MMP9,Wnt3a,β-catenin mRNA and protein levels of Kaempferol low-dose group and Kaempferol high-dose group were significantly lower than those of control group,while apoptosis index was significantly higher than that in control group(P<0.05).Tumor volume[(180.56±21.56)mm3],mass[(0.21±0.03)g],Cyclin D1,Ki67,MMP2,MMP9,Wnt3a,β-catenin mRNA and protein levels in Kaempferol high-dose group were significantly lower than those of Kaempferol low-dose group,while apoptosis index[(17.43±1.89)%]was significantly higher than that of Kaempferol low-dose group[(10.05±1.05)%,P<0.05]. CD4^(+),CD4^(+)/CD8^(+),IFN-γ and IL-2 levels in three groups of mice were significantly different(P<0.05). Levels of CD4^(+),CD4^(+)/CD8^(+),IFN-γ and IL-2 in Kaempferol low-dose group and Kaempferol high-dose group were significantly higher than those of control group(P<0.05). Levels of CD4^(+)[(23.81±1.36)%],CD4^(+)/CD8^(+)(1.51±0.13),IFN-γ[(9.15±1.12)ng/ml]and IL-2[(1.78±0.11)ng/ml]in Kaempferol highdose group were significant higher than that

关 键 词：前列腺癌 山柰酚 Wnt/β-catenin途径 免疫抑制 T淋巴细胞 

分 类 号：R73-362[医药卫生—肿瘤]