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GK-1肽可降低小鼠乳腺癌模型中的肿瘤生长、减轻转移负担并提高生存率。

GK-1 peptide reduces tumor growth, decreases metastatic burden, and increases survival in a murine breast cancer model.

作者信息

Torres-García D, Pérez-Torres A, Manoutcharian K, Orbe U, Servín-Blanco R, Fragoso G, Sciutto E

机构信息

Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Av. Universidad 3000, 04510 Mexico City, Mexico.

Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México, Av. Universidad 3000, 04510 Mexico City, Mexico.

出版信息

Vaccine. 2017 Oct 9;35(42):5653-5661. doi: 10.1016/j.vaccine.2017.08.060. Epub 2017 Sep 7.

Abstract

GK-1 is a parasite-derived peptide adjuvant of 18 amino acid-length that enhances T-cell function and increases survival in B16-F10 melanoma tumor-bearing mice. This study was designed to evaluate in vivo the antitumor efficacy of GK-1 on 4T1 mouse mammary carcinoma. BALB/c mice with palpable primary tumors were weekly intravenously injected three times with saline solution or three different concentrations (10, 50, or 100μg per mouse) of GK-1. GK-1 significantly increased lifespan (p<0.0001) and reduced the primary tumor weight (p=0.014) and volume (p<0.0001) with respect to control mice, with no statistically significant differences among GK-1 doses. At the primary tumor, we found increased necrotic areas associated with a reduction in tumor mass, as well as an increase in the antitumor cytokine IL-12. Especially encouraging is the ability of GK-1 to reduce the number of lung metastasis (p=0.006) disregarding the dose used. The participation of IL-6 in metastasis development and the decreased levels of CCL-2, CCL-3, TNF-α, CXCL-9, GM-CSF, and b-FGF found in lungs of GK-1-treated mice is discussed. Our study supports the effectiveness of GK-1 as an antineoplastic agent that merits further exploration in combination with other therapeutic approaches in future translational studies.

摘要

GK-1是一种长度为18个氨基酸的寄生虫衍生肽佐剂,可增强T细胞功能并延长携带B16-F10黑色素瘤肿瘤的小鼠的生存期。本研究旨在评估GK-1对4T1小鼠乳腺癌的体内抗肿瘤疗效。对可触及原发性肿瘤的BALB/c小鼠每周静脉注射三次生理盐水或三种不同浓度(每只小鼠10、50或100μg)的GK-1。与对照小鼠相比,GK-1显著延长了生存期(p<0.0001),并减轻了原发性肿瘤的重量(p=0.014)和体积(p<0.0001),不同剂量的GK-1之间无统计学显著差异。在原发性肿瘤处,我们发现坏死区域增加,伴有肿瘤质量减少,以及抗肿瘤细胞因子IL-12增加。特别令人鼓舞的是,无论使用何种剂量,GK-1都能减少肺转移的数量(p=0.006)。本文还讨论了IL-6在转移发展中的作用以及在接受GK-1治疗的小鼠肺中发现的CCL-2、CCL-3、TNF-α、CXCL-9、GM-CSF和b-FGF水平降低的情况。我们的研究支持GK-1作为一种抗肿瘤药物的有效性,值得在未来的转化研究中与其他治疗方法联合进行进一步探索。

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