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没食子酸甲酯通过诱导细胞凋亡和抗血管生成抑制犬乳腺肿瘤。

Methyl Gallate Suppresses Canine Mammary Gland Tumors by Inducing Apoptosis and Anti-angiogenesis.

机构信息

College of Veterinary Medicine, Jeonbuk National University, Iksan, Republic of Korea.

College of Veterinary Medicine, Jeonbuk National University, Iksan, Republic of Korea

出版信息

Anticancer Res. 2024 Oct;44(10):4317-4326. doi: 10.21873/anticanres.17261.

DOI:10.21873/anticanres.17261
PMID:39348974
Abstract

BACKGROUND/AIM: Methyl gallate (MG), a plant phenolic compound, has known anticancer properties. However, its effects on canine mammary gland tumors (CMTs) are unclear. This study evaluated the impact of MG on cell viability, migration, and apoptosis in two CMT cell lines.

MATERIALS AND METHODS

CMT-U27 and CF41.mg cells were used. In vitro experiments included MTT and scratch assays, Annexin-V/propidium iodide double staining, immunocytochemistry, and western blot analyses. An in vivo CMT xenograft mouse model was also used to observe the effects of MG on tumor growth and vasculature. Immunohistochemistry was performed to analyze vessel density and apoptosis in tumor tissues. Cell migration and tube formation assays with canine aortic endothelial cells assessed the anti-angiogenic effects of MG.

RESULTS

Data showed a significant decrease in cell viability and migration in both CMT cell lines after 24 h exposure to various MG concentrations. MG treatment induced dose-dependent apoptotic cell death and elevated cleaved caspase-3 expression. In vivo experiments confirmed tumor growth suppression 21 days post-treatment with 40 mg/kg MG. Tumor tissues displayed increased cleaved caspase-3 and reduced vessel density. MG also inhibited cell migration and disrupted tube formation in canine endothelial cells.

CONCLUSION

MG has potential as an anticancer drug for CMTs by promoting apoptotic cell death and reducing angiogenesis, highlighting its therapeutic promise.

摘要

背景/目的:没食子酸甲酯(MG)是一种植物酚类化合物,具有已知的抗癌特性。然而,其对犬乳腺肿瘤(CMTs)的影响尚不清楚。本研究评估了 MG 对两种 CMT 细胞系的细胞活力、迁移和凋亡的影响。

材料和方法

使用 CMT-U27 和 CF41.mg 细胞。体外实验包括 MTT 和划痕实验、Annexin-V/碘化丙啶双染色、免疫细胞化学和 Western blot 分析。还使用了犬乳腺肿瘤异种移植小鼠模型来观察 MG 对肿瘤生长和血管生成的影响。免疫组织化学用于分析肿瘤组织中的血管密度和细胞凋亡。用犬主动脉内皮细胞进行细胞迁移和管形成实验评估 MG 的抗血管生成作用。

结果

数据显示,两种 CMT 细胞系在暴露于不同 MG 浓度 24 小时后,细胞活力和迁移明显下降。MG 处理诱导了剂量依赖性的凋亡细胞死亡和 cleaved caspase-3 表达的增加。体内实验证实,用 40mg/kg MG 治疗 21 天后可抑制肿瘤生长。肿瘤组织中 cleaved caspase-3 增加,血管密度降低。MG 还抑制了犬内皮细胞的迁移和管形成。

结论

MG 通过促进凋亡细胞死亡和减少血管生成,具有作为犬乳腺肿瘤治疗药物的潜力,这突出了其治疗前景。

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