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用于研究大豆衍生肽芦那辛抗癌作用的同基因黑色素瘤和非小细胞肺癌小鼠模型的验证

Validation of syngeneic mouse models of melanoma and non-small cell lung cancer for investigating the anticancer effects of the soy-derived peptide Lunasin.

作者信息

Devapatla Bharat, Shidal Chris, Yaddanapudi Kavitha, Davis Keith R

机构信息

Department of Pharmacology and Toxicology, University of Louisville School of Medicine, , Louisville, KY, 40402, USA.

Department of Pharmacology and Toxicology, University of Louisville School of Medicine, , Louisville, KY, 40402, USA; Department of Biology and Biotechnology Program, Indiana University, Bloomington, IN, 47405, USA.

出版信息

F1000Res. 2016 Oct 4;5:2432. doi: 10.12688/f1000research.9661.2. eCollection 2016.

DOI:10.12688/f1000research.9661.2
PMID:28299174
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5325107/
Abstract

: Lunasin is a naturally occurring peptide present in soybean that has both chemopreventive and therapeutic activities that can prevent cellular transformation and inhibit the growth of several human cancer types. Recent studies indicate that Lunasin has several distinct potential modes of action including suppressing integrin signaling and epigenetic effects driven by modulation of histone acetylation. In addition to direct effects on cancer cells, Lunasin also has effects on innate immunity that may contribute to its ability to inhibit tumor growth . Standard assays for cell proliferation and colony formation were used to assess Lunasin's activity against murine Lewis lung carcinoma (LLC) and B16-F0 melanoma cells.  Lunasin's activity was assessed by comparing the growth of tumors initiated by subcutaneous implantation of LLC or B16-F0 cells in Lunasin-treated and untreated C57BL/6 mice. Lunasin was found to inhibit growth of murine LLC cells and murine B16-F0 melanoma cells and in wild-type C57BL/6 mice.  The effects of Lunasin in these two mouse models were very similar to those previously observed in studies of human non-small cell lung cancer and melanoma cell lines. We have now validated two established syngeneic mouse models as being responsive to Lunasin treatment.  The validation of these two syngeneic models will allow detailed studies on the combined therapeutic and immune effects of Lunasin in a fully immunocompetent mouse model.

摘要

芦那辛是大豆中天然存在的一种肽,具有化学预防和治疗活性,可预防细胞转化并抑制多种人类癌症类型的生长。最近的研究表明,芦那辛有几种不同的潜在作用模式,包括抑制整合素信号传导以及由组蛋白乙酰化调节驱动的表观遗传效应。除了对癌细胞有直接作用外,芦那辛对先天免疫也有影响,这可能有助于其抑制肿瘤生长的能力。使用细胞增殖和集落形成的标准测定法来评估芦那辛对小鼠刘易斯肺癌(LLC)和B16-F0黑色素瘤细胞的活性。通过比较在经芦那辛处理和未处理的C57BL/6小鼠中皮下植入LLC或B16-F0细胞引发的肿瘤生长情况,来评估芦那辛的活性。发现芦那辛可抑制小鼠LLC细胞和小鼠B16-F0黑色素瘤细胞在野生型C57BL/6小鼠中的生长。芦那辛在这两种小鼠模型中的作用与先前在人类非小细胞肺癌和黑色素瘤细胞系研究中观察到的作用非常相似。我们现在已经验证了两种已建立的同基因小鼠模型对芦那辛治疗有反应。这两种同基因模型的验证将允许在完全免疫 competent 的小鼠模型中对芦那辛的联合治疗和免疫作用进行详细研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3df3/5325108/c00e13f381d7/f1000research-5-11815-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3df3/5325108/144ffb6be1bb/f1000research-5-11815-g0000.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3df3/5325108/c00e13f381d7/f1000research-5-11815-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3df3/5325108/144ffb6be1bb/f1000research-5-11815-g0000.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3df3/5325108/c00e13f381d7/f1000research-5-11815-g0001.jpg

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