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可透析白细胞提取物 Transferon 抑制前列腺癌小鼠模型中的肿瘤生长和脑转移。

The dialyzable leukocyte extract Transferon inhibits tumor growth and brain metastasis in a murine model of prostate cancer.

机构信息

Unidad de Desarrollo e Investigación en Bioprocesos (UDIBI), Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México, Mexico.

Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, Mexico.

出版信息

Biomed Pharmacother. 2018 May;101:938-944. doi: 10.1016/j.biopha.2018.03.012. Epub 2018 Mar 22.

Abstract

Prostate cancer (PCa) is the second most frequently diagnosed cancer in men worldwide. Dialyzed Leukocyte Extracts (DLEs) are heterogeneous mixtures of low-molecular-weight peptides that improve clinical responses in various diseases. Here, we analyzed the effects of Transferon, a commercial DLE with characterized active pharmaceutical ingredient and proven batch-to-batch reproducibility, in preclinical models of PCa. We employed v-Src-transformed murine prostate epithelial (PEC-Src) cells, which recapitulate the transcriptional profiles in human PCa, can be grown in immunocompetent mice, and consistently form bone and brain metastases. In vitro, Transferon did not induce cytotoxicity nor alterations in migration /invasion of PEC-Src cells. In vivo, Transferon reduced metastatic dissemination after intracardiac injection of PEC-Src and inhibited tumor growth of subcutaneous isotransplants. The antineoplastic effect of Transferon correlated with changes in tumor infiltration, increased serum concentrations of IL-12 and CXCL1, and reduced levels of VEGF. Our results suggest that the antineoplastic effect produced by Transferon is due to its immunomodulatory activity and not by a direct effect on cancer cells, and indicate that Transferon could be beneficial as adjuvant therapy in PCa patients.

摘要

前列腺癌(PCa)是全球男性中第二大常见的癌症。透析白细胞提取物(DLEs)是低分子量肽的不均匀混合物,可改善各种疾病的临床反应。在这里,我们分析了 Transferon 的作用,Transferon 是一种具有特征性活性药物成分和经过验证的批间重现性的商业 DLE,在 PCa 的临床前模型中进行了分析。我们使用 v-Src 转化的鼠前列腺上皮(PEC-Src)细胞,该细胞再现了人类 PCa 的转录谱,可以在免疫功能正常的小鼠中生长,并且一致形成骨和脑转移。在体外,Transferon 既不会诱导细胞毒性,也不会改变 PEC-Src 细胞的迁移/侵袭。在体内,Transferon 减少了 PEC-Src 心内注射后的转移扩散,并抑制了皮下同系移植瘤的生长。Transferon 的抗肿瘤作用与肿瘤浸润的变化、血清中 IL-12 和 CXCL1 浓度的增加以及 VEGF 水平的降低有关。我们的结果表明,Transferon 产生的抗肿瘤作用是由于其免疫调节活性,而不是直接作用于癌细胞,这表明 Transferon 可作为 PCa 患者的辅助治疗有益。

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