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基于牛乳铁蛋白和/或胞壁酰二肽联合治疗对荷瘤小鼠的抗肿瘤和免疫调节效力。

Anti-neoplastic and immunomodulatory potency of co-treatment based on bovine lactoferrin and/or muramyl dipeptide in tumor-bearing mice.

作者信息

Ibrahim Hany M, Mohamed Azza H, Salem Mohamed L, Osman Gamalat Y, Morsi Dalia S

机构信息

Zoology Department, Faculty of Science, Menoufia University, Shibin El Kom 32511, Egypt.

Zoology Department, Faculty of Science, Tanta University, Tanta 31527, Egypt.

出版信息

Toxicol Res (Camb). 2020 Apr 24;9(2):137-147. doi: 10.1093/toxres/tfaa012. eCollection 2020 Apr.

Abstract

The current study investigates anti-neoplastic and immunomodulatory activities of co-treatment based on bovine lactoferrin (bLF) and/or muramyl dipeptide (MDP) with or without cisplatin (Cis) in tumor-bearing mice. In the present study, bLF (100 mg/kg; orally) and MDP (0.5 mg/kg; subcutaneously) was administered alone or together. MDP or bLF was co-treated with Cis (1 mg/kg; intraperitoneally) in mice-bearing Ehrlich solid carcinoma. Tumor size, tumor mass proliferation, apoptosis using immunohistochemistry, the alteration in spleen cell proliferation, phenotype using flow cytometry and white blood cells total and differential counts were detected. Treatment with Cis or (bLF and MDP) significantly reduced tumor size, upregulated the pro-apoptotic p53 expression and downregulated the anti-apoptotic Bcl-2 and proliferative marker PCNA expression compared to non-treated tumor-bearing animals. Moreover, co-treatment of MDP and Cis significantly potentiated the reduction of the tumor size, downregulated the Bcl-2 and PCNA expression and upregulated the p53 expression compared to Cis-treated animals. While bLF and Cis co-treatment positively controlled PCNA and p53 expression compared to tumor-bearing animals, it significantly potentiated the reduction of the tumor size and downregulated the Bcl-2 expression compared to Cis-treated animals. Co-treatment of (bLF and MDP), (bLF and Cis) or (MDP and Cis) increased the spleen cell proliferation and altered the immunological profile of the CD3CD4, CD3CD8, CD3CD4CD69, CD3CD8CD69 and CD11bLy6G cells to achieve better immune response against tumor. In conclusion, co-treatments based on bLF and/or MDP are promising therapies against cancer, through their potency to control proliferation, enhance apoptosis and improve the immune status against tumor cells.

摘要

本研究调查了在荷瘤小鼠中,基于牛乳铁蛋白(bLF)和/或胞壁酰二肽(MDP)联合或不联合顺铂(Cis)治疗的抗肿瘤和免疫调节活性。在本研究中,单独或联合给予bLF(100mg/kg;口服)和MDP(0.5mg/kg;皮下注射)。在荷艾氏实体癌小鼠中,MDP或bLF与Cis(1mg/kg;腹腔注射)联合治疗。检测肿瘤大小、肿瘤块增殖、采用免疫组织化学检测细胞凋亡、脾细胞增殖变化、采用流式细胞术检测表型以及白细胞总数和分类计数。与未治疗的荷瘤动物相比,Cis或(bLF和MDP)治疗显著减小了肿瘤大小,上调促凋亡p53表达,下调抗凋亡Bcl-2和增殖标志物PCNA表达。此外,与Cis治疗的动物相比,MDP和Cis联合治疗显著增强了肿瘤大小的减小,下调了Bcl-2和PCNA表达,上调了p53表达。与荷瘤动物相比,bLF和Cis联合治疗可正向调控PCNA和p53表达,与Cis治疗的动物相比,它显著增强了肿瘤大小的减小并下调了Bcl-2表达。(bLF和MDP)、(bLF和Cis)或(MDP和Cis)联合治疗增加了脾细胞增殖,并改变了CD3CD4、CD3CD8、CD3CD4CD69、CD3CD8CD69和CD11bLy6G细胞的免疫谱,以实现对肿瘤更好的免疫反应。总之,基于bLF和/或MDP的联合治疗有望成为抗癌疗法,因为它们具有控制增殖、增强细胞凋亡和改善针对肿瘤细胞的免疫状态的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fcf/7233322/44891db4adeb/tfaa012ga.jpg

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