雷公藤甲素给药抑制同种异体 TRAMP-C1 前列腺癌小鼠的癌细胞生长，与体内免疫平衡相关。

Rutaecarpine administration inhibits cancer cell growth in allogenic TRAMP-C1 prostate cancer mice correlating with immune balance in vivo.

机构信息

Department of Food Science and Biotechnology, National Chung Hsing University, 250 Kuokuang Road, Taichung 40227, Taiwan.

出版信息

Biomed Pharmacother. 2021 Jul;139:111648. doi: 10.1016/j.biopha.2021.111648. Epub 2021 May 1.

DOI:10.1016/j.biopha.2021.111648

PMID:33945915

Abstract

BACKGROUND

Rutaecarpine (Rut) is a plant alkaloid abundant in Euodia ruticarpa which is a Chinese herbal medicine used for treating various cancers. However, the Rut administration effect on prostate cancer in vivo remains unclear.

AIM

In the present study we established an allogenic TRAMP-C1 prostate cancer mouse model to evaluate the Rut administration effect and mechanism in vivo.

METHODS

To unravel the Rut administration effect on prostate cancer in vivo, C57BL/6J male mice (8 weeks old) were randomly grouped (n = 9), subcutaneously loaded with TRAMP-C1 prostate cancer cells and immediately given daily by gavage with Rut dissolved in soybean oil at 7 mg (low dose), 35 mg (medium dose), and 70 mg/kg b.w./day (high dose) for successive 39 days.

RESULTS

Rut administration significantly and dose-dependently reduced both tumor volume and solid prostate cancer weight in allogenic TRAMP-C1 male mice. Rut administration markedly increased (TNF-α+IFN-γ) (Th1-)/IL-10 (Th2-) cytokine secretion ratios by splenocytes and TNF-α (M1-)/IL-10 (M2-) cytokine secretion ratios by macrophages as compared to those of dietary control group, suggesting that Rut administration in vivo regulates the immune balance toward Th1- and M1-polarized characteristics. Decreased CD19, CD4 and CD8 lymphocytes in the peripheral blood of allogenic TRAMP-C1 mice were significantly elevated by Rut administration. Tumor weights positively correlated with TNF-α secretions by splenocytes, suggesting that there is a tumor cachexia in the tumor-bearing mice. Tumor weights negatively correlated with IgG (Th1-antibody) levels in the sera, suggesting that Th1-polarized immune balance may inhibit prostate cancer cell growth.

CONCLUSIONS

Our results evidenced that Rut administration suppresses prostate cancer cell growth in mice subcutaneously loaded with TRAMP-C1 cells and correlated the anti-cancer effects with Th1-polarized immune balance in vivo.

摘要

背景

荷叶碱（Rut）是一种植物生物碱，在芸香科吴茱萸中含量丰富，吴茱萸是一种中草药，用于治疗各种癌症。然而，荷叶碱对体内前列腺癌的作用尚不清楚。

目的

本研究建立了同种异体 TRAMP-C1 前列腺癌小鼠模型，以评估体内荷叶碱的作用和机制。

方法

为了揭示荷叶碱对体内前列腺癌的作用，将 8 周龄 C57BL/6J 雄性小鼠随机分组（n=9），皮下接种 TRAMP-C1 前列腺癌细胞，立即给予每天灌胃溶于大豆油的荷叶碱，剂量分别为 7mg（低剂量）、35mg（中剂量）和 70mg/kg b.w./天（高剂量），连续 39 天。

结果

荷叶碱给药显著且剂量依赖性地降低了同种异体 TRAMP-C1 雄性小鼠的肿瘤体积和实体前列腺癌重量。荷叶碱给药明显增加了脾细胞中（TNF-α+IFN-γ）（Th1-）/IL-10（Th2-）细胞因子分泌比率和巨噬细胞中 TNF-α（M1-）/IL-10（M2-）细胞因子分泌比率，与饮食对照组相比，提示荷叶碱体内给药调节免疫平衡向 Th1-和 M1-极化特征。同种异体 TRAMP-C1 小鼠外周血中的 CD19、CD4 和 CD8 淋巴细胞减少，经荷叶碱给药后显著升高。肿瘤重量与脾细胞中 TNF-α分泌呈正相关，提示荷瘤小鼠存在恶病质。肿瘤重量与血清中 IgG（Th1 抗体）水平呈负相关，提示 Th1 极化免疫平衡可能抑制前列腺癌细胞生长。