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提取物可减小小鼠乳腺癌模型中的原发性肿瘤,但对黑色素瘤无效。

Extract Decreases the Primary Tumor in a Murine Breast Cancer Model but Not in Melanoma.

作者信息

Lasso Paola, Rojas Laura, Arévalo Cindy, Urueña Claudia, Murillo Natalia, Barreto Alfonso, Costa Geison M, Fiorentino Susana

机构信息

Grupo de Inmunobiología y Biología Celular, Pontificia Universidad Javeriana, Bogotá 110231, Colombia.

Grupo de Investigación en Fitoquímica, Pontificia Universidad Javeriana, Bogotá 110231, Colombia.

出版信息

Cancers (Basel). 2022 Nov 1;14(21):5383. doi: 10.3390/cancers14215383.

Abstract

The main limits of current antitumor therapies are chemoresistance, relapses, and toxicity that impair patient quality of life. Therefore, the discovery of therapeutic alternatives, such as adjuvants to conventional therapy that modulate the intracellular oxidation state or the immune response, remains a challenge. Owing to traditional medicine, several uses of plants are known, indicating a promising antitumor and immunomodulatory effect. We evaluated the effect of ethanolic extract of in vitro and in vivo in models of 4T1 breast cancer and B16-F10 melanoma. In vitro evaluations with both cell lines showed that the extract has cytotoxic activity and induces apoptotic cell death. However, its effect on ROS production and glucose uptake was opposite. In vivo, only in the 4T1 model, a significant decrease in tumor size was found in animals treated with the extract, accompanied by an increase in dendritic cells and activated CD8 T cells, and a decrease in myeloid-derived suppressor-like cells (MDSC-LC) and Tregs in the tumor microenvironment. These results suggest that extract antagonistically regulates tumor metabolism of 4T1 vs. B16-F10, impacting the tumor microenvironment and effective antitumor immune response, leading to a reduction in 4T1 tumor size but not on B16-F10.

摘要

当前抗肿瘤疗法的主要局限性在于化疗耐药性、复发以及影响患者生活质量的毒性。因此,发现治疗替代方案,如调节细胞内氧化状态或免疫反应的传统疗法佐剂,仍然是一项挑战。由于传统医学,植物的多种用途已为人所知,显示出有前景的抗肿瘤和免疫调节作用。我们在4T1乳腺癌和B16-F10黑色素瘤模型中评估了[植物名称]乙醇提取物的体内外作用。对这两种细胞系的体外评估表明,该提取物具有细胞毒性活性并诱导凋亡性细胞死亡。然而,其对活性氧生成和葡萄糖摄取的影响却相反。在体内,仅在4T1模型中,发现用该提取物处理的动物肿瘤大小显著减小,同时肿瘤微环境中的树突状细胞和活化的CD8 T细胞增加,髓系来源的抑制样细胞(MDSC-LC)和调节性T细胞减少。这些结果表明,[植物名称]提取物对4T1和B16-F10的肿瘤代谢具有拮抗调节作用,影响肿瘤微环境和有效的抗肿瘤免疫反应,导致4T1肿瘤大小减小,但对B16-F10无效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4402/9656114/8d9ebc3b572f/cancers-14-05383-g001.jpg

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