6 Iodo-delta lactone inhibits angiogenesis in human HT29 colon adenocarcinoma xenograft.

IF 3
Romina Oglio , Federico Buschittari , Leonardo Salvarredi , Jennifer Michaux , Carla Rodriguez , Marina Perona , Alejandra Dagrosa , Guillermo Juvenal , Lisa Thomasz
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引用次数: 1

Abstract

Introduction

Several studies have shown the antiproliferative effect of iodine and 5‑hydroxy-6 iodo-eicosatrienoic delta lactone (IL-δ) on diverse tissues. It was demonstrated that molecular iodine (I2) and IL-δ, but not iodide (I), exerts anti-neoplastic actions in different cancers. The underlying mechanism through which IL-δ inhibits tumor growth remains unclear. The aim of this study was to analyze the effect of IL-δ on tumor growth and angiogenesis in human HT29 colorectal cancer xenografts.

Methodology and Results

HT29 cells were injected subcutaneously into the flanks of nude mice and IL-δ was i.p. injected at a dose of 15 μg three days a week. IL-δ treatment in HT29 xenografts showed time-dependent inhibition of tumor growth, decrease of mitosis and PCNA expression (p < 0.05), increase of P27 expression and Caspase 3 activity after 18 days of treatment (p < 0.05). To assess tumor Microvessel Densities (MVD), CD31 staining by immunohistochemistry was analyzed. IL-δ treatment decreased MVD by 17% and 30% after 18 and 30 days respectively (p < 0.05), as well as it decreased VEGF and VEGF-R2 expression (p < 0.05). Additionally, our findings demonstrated that IL-δ increased VEGF-R1 and Ang-1 mRNA levels (p < 0.01).

Conclusion

The antitumor efficacy of IL-δ in vivo involves inhibition of cell proliferation as well as induction of apoptosis. IL-δ has also anti-angiogenic effect associated with VEGF and VEGF-R2 downregulation followed by Ang-1 and VEGF-R1 increased expression. High levels of Ang-1 would contribute to mature vessel stabilization and maintenance while VEGF-R1 increase would produce anti-proliferative effect on endothelial cells.

碘- δ内酯抑制人HT29结肠癌异种移植血管生成。
一些研究表明,碘和5 -羟基-6碘-二十碳三烯δ内酯(IL-δ)对多种组织具有抗增殖作用。结果表明,分子碘(I2)和IL-δ在不同肿瘤中发挥抗肿瘤作用,而碘(I−)不起作用。IL-δ抑制肿瘤生长的潜在机制尚不清楚。本研究的目的是分析IL-δ对人HT29结直肠癌异种移植瘤生长和血管生成的影响。方法与结果将sht29细胞皮下注射至裸鼠侧腹,IL-δ以15 μg的剂量内注射,每周3天。IL-δ处理HT29异种移植物显示出时间依赖性的肿瘤生长抑制,有丝分裂和PCNA表达降低(p <0.05),治疗18 d后P27表达和Caspase 3活性升高(p <0.05)。免疫组化CD31染色评估肿瘤微血管密度(MVD)。IL-δ处理18天和30天后MVD分别降低17%和30% (p <0.05),同时降低VEGF和VEGF- r2的表达(p <0.05)。此外,我们的研究结果表明,IL-δ增加了VEGF-R1和Ang-1 mRNA水平(p <0.01)。结论IL-δ在体内的抗肿瘤作用包括抑制细胞增殖和诱导细胞凋亡。IL-δ也具有抗血管生成作用,与VEGF和VEGF- r2下调相关,随后是Ang-1和VEGF- r1表达升高。高水平的Ang-1有助于成熟血管的稳定和维持,而VEGF-R1的增加会对内皮细胞产生抗增殖作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Prostaglandins, leukotrienes, and essential fatty acids
Prostaglandins, leukotrienes, and essential fatty acids Clinical Biochemistry, Endocrinology, Diabetes and Metabolism
CiteScore
5.30
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0.00%
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审稿时长
64 days
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