关键词: Ehrlich solid carcinoma Trichinella spiralis antigen anti‐tumor apoptosis biotherapy crude larval extract

Mesh : Animals Trichinella spiralis / drug effects Mice Larva / drug effects Carcinoma, Ehrlich Tumor / drug therapy pathology immunology Apoptosis / drug effects Cell Proliferation / drug effects Disease Models, Animal Antigens, Helminth / immunology Caspase 3 / metabolism bcl-2-Associated X Protein / metabolism Ki-67 Antigen / metabolism Proto-Oncogene Proteins c-bcl-2 / metabolism genetics Tumor Necrosis Factor-alpha / metabolism Antineoplastic Agents / pharmacology therapeutic use Female Immunohistochemistry

来  源:   DOI:10.1111/pim.13035

Abstract:
Trichinella spiralis (T. spiralis) is an immunomodulating parasite that can adversely affect tumor growth and extend host lifespan. The aim of this study was to elucidate the mechanisms by which T. spiralis larval antigens achieve this effect using Ehrlich solid carcinoma (ESC) murine model. Assessment was done by histopathological and immunohistochemical analysis of caspase-3, TNF-α, Ki-67 and CD31. Additionally, Bcl2 and Bcl2-associated protein X (Bax) relative gene expression was assessed by molecular analysis for studying the effect of T. spiralis crude larval extract (CLE) antigen on tumor necrosis, apoptosis, cell proliferation and angiogenesis. We found that both T. spiralis infection and CLE caused a decrease in the areas of necrosis in ESC. Moreover, they led to increased apoptosis through activation of caspase-3, up-regulation of pro-apoptotic gene, Bax and down-regulation of anti-apoptotic gene, Bcl2. Also, T. spiralis infection and CLE diminished ESC proliferation, as evidenced by decreasing Ki-67. T. spiralis infection and CLE were able to suppress the development of ESC by inhibiting tumor proliferation, inducing apoptosis and decreasing tumor necrosis, with subsequent decrease in tumor metastasis. T. spiralis CLE antigen may be considered as a promising complementary immunotherapeutic agent in the treatment of cancer.
摘要:
旋毛虫(T.spiralis)是一种免疫调节寄生虫,可对肿瘤生长产生不利影响并延长宿主寿命。这项研究的目的是阐明使用Ehrlich实体癌(ESC)小鼠模型的旋毛虫幼虫抗原实现这种作用的机制。通过caspase-3,TNF-α的组织病理学和免疫组织化学分析进行评估,Ki-67和CD31。此外,通过分子分析评估Bcl2和Bcl2相关蛋白X(Bax)的相对基因表达,以研究旋毛虫粗幼虫提取物(CLE)抗原对肿瘤坏死的影响,凋亡,细胞增殖和血管生成。我们发现旋毛虫感染和CLE均导致ESC坏死面积减少。此外,它们通过激活caspase-3,上调促凋亡基因,导致凋亡增加,Bax与抗凋亡基因下调,Bcl2。此外,旋毛虫感染和CLE减少了ESC增殖,如Ki-67降低所证明。旋毛虫感染和CLE能够通过抑制肿瘤增殖来抑制ESC的发展,诱导细胞凋亡和减少肿瘤坏死,随后肿瘤转移减少。旋毛虫CLE抗原可被认为是治疗癌症的有希望的互补免疫治疗剂。
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