首页|竹节香附素A通过抑制程序性细胞死亡配体1调节前列腺癌小鼠肿瘤免疫并发挥抗肿瘤作用

竹节香附素A通过抑制程序性细胞死亡配体1调节前列腺癌小鼠肿瘤免疫并发挥抗肿瘤作用

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目的:探讨竹节香附素A(RA)对前列腺癌移植瘤模型小鼠的治疗效果及潜在作用机制.方法:(1)采用Western blot实验检测不同浓度RA(0、0.5、1、2和4 µmol/L)对前列腺癌细胞系PC-3、DU145和RM-1中程序性细胞死亡配体1(PD-L1)蛋白表达的影响.(2)将30只C57BL/6J小鼠随机分为空白对照组、低剂量RA组和高剂量RA组,每组10只.低、高剂量RA组小鼠分别腹腔注射2和4 mg/kg RA,连续给药24 d.记录小鼠体重,统计各组小鼠肿瘤体积和瘤重;采用免疫组化实验检测小鼠肿瘤组织中Ki67和PD-L1蛋白表达;通过流式细胞术检测肿瘤组织中CD8+T细胞、CD4+T细胞和调节性T细胞(Treg)比例,以及干扰素γ(IFN-γ)和颗粒酶B(GzmB)水平.结果:(1)RA处理显著降低PC-3、DU145和RM-1细胞中PD-L1表达水平(P<0.05或P<0.01).(2)在体内实验中,RA处理组小鼠的肿瘤体积和重量显著减小,同时肿瘤组织中Ki67和PD-L1的表达水平显著降低(P<0.05或P<0.01).此外,RA处理显著增加小鼠肿瘤内CD8+T细胞和CD4+T细胞的比例,提高IFN-γ和GzmB水平,同时减少活化的Treg数量(P<0.05或P<0.01).结论:RA对前列腺癌小鼠肿瘤生长具有较好抑制作用,其机制可能与抑制PD-L1表达、增加肿瘤浸润T细胞及抑制Treg有关.
Raddeanin A regulates tumor immunity and exerts anti-tumor effects in prostate cancer mice by inhibiting programmed cell death ligand 1
AIM:To investigate the therapeutic effect of raddeanin A(RA)on prostate cancer xenograft mouse model,and to explore its potential mechanisms.METHODS:(1)Western blot analysis was used to investigate the effects of different concentrations(0,0.5,1,2 and 4 µmol/L)of RA on the expression of programmed cell death li-gand 1(PD-L1)protein in prostate cancer cell lines PC-3,DU145 and RM-1.(2)Thirty C57BL/6J mice were randomly divided into blank group,low-dose RA group,and high-dose RA group,with 10 mice in each group.The mice in low-and high-dose RA groups were intraperitoneally injected with 2 and 4 mg/kg RA continuously for 24 d,respectively.Mouse body weight was recorded,and tumor volume and weight were measured.Immunohistochemistry experiments were con-ducted to detect the expression of Ki67 and PD-L1 proteins in mouse tumor tissues.Flow cytometry was used to determine the percentages of CD8+T cells,CD4+T cells and regulatory T cells(Treg),as well as the levels of interferon-γ(IFN-γ)and granzyme B(GzmB)in tumor tissues.RESULTS:Treatment with RA significantly reduced the expression of PD-L1 in PC-3,DU145 and RM-1 cells(P<0.05 or P<0.01).In vivo experiments showed that RA treatment led to significant decreases in tumor volume and weight(P<0.05 or P<0.01).Additionally,the expression levels of Ki67 and PD-L1 in tu-mor tissues were significantly reduced(P<0.05 or P<0.01).Furthermore,RA treatment significantly increased the per-centages of CD8+T cells and CD4+T cells within mouse tumors,elevated the levels of IFN-γ and GzmB,and reduced the number of activated Treg(P<0.05 or P<0.01).CONCLUSION:The RA exhibits potent inhibitory effects on tumor growth in a prostate cancer xenograft mouse model.Its mechanism may be associated with the inhibition of PD-L1 expres-sion,increased infiltration of tumor-infiltrating T cells,and suppression of Treg.

Prostate cancerraddeanin Aprogrammed cell death ligand 1T-lymphocytes

余本坚、梁世佳、宋旭、张圣熙、张耘

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上海中医药大学附属上海市第七人民医院,上海 200137

前列腺癌 竹节香附素A 程序性细胞死亡配体1 T淋巴细胞

浦东新区临床中医高原学科建设资助"十四五"中医特色专科中医男科建设项目浦东新区卫生系统重点亚专科建设项目

YC-2023-0609ZYTSZK1-4PWZy2022-02

2024

中国病理生理杂志
中国病理生理学会

中国病理生理杂志

CSTPCD北大核心
影响因子:1.065
ISSN:1000-4718
年,卷(期):2024.40(9)