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L. 多糖增强树突状细胞瘤苗对乳腺癌的免疫疗效。

L. polysaccharides enhance the immune efficacy of dendritic cell vaccine for breast cancer.

机构信息

Department of Pharmaceutical Engineering, College of Life Science & Biotechnology, Heilongjiang August First Land Reclamation University, Daqing High-Tech Industrial Development Zone, 163319, P. R. China.

Department of gynaecology and obstetrics, Daqing Oilfield Hospital, Daqing 163311, P. R China.

出版信息

Food Funct. 2021 May 11;12(9):4046-4059. doi: 10.1039/d0fo02522d.

Abstract

Previous studies have reported that Portulaca oleracea L. polysaccharides (POL-P3b) is an immunoregulatory agent. However, few studies exist on POL-P3b as a novel immune adjuvant in combination with the DC vaccine for breast cancer treatment. In this work, a DC vaccine loaded with mouse 4T1 tumor cell antigen was prepared to evaluate the properties of POL-P3b in inducing the maturation and function of DC derived from mouse bone marrow, and then to investigate the effect of the DC vaccine combined with POL-P3b on breast cancer in vivo and in vitro. Morphological changes of DC were observed using scanning electron microscopy. Phenotypic and functional analyses of DC were detected by flow cytometry and allogeneic lymphocyte reaction. Cytokine levels in the DC culture supernatant were detected by ELISA. Western blotting analysis was used for the protein expression of TLR4, MyD88 and NF-κB. Apoptosis detection and protein expression of the tumor tissue were analyzed by TUNEL staining and immunohistochemistry, respectively. The security of POL-P3b was evaluated by the detection of hematological and blood biochemical indicators and pathological analysis for tissues. POL-P3b can induce DC activation and maturation, which is attributed to increasing the specific anti-tumor immune response, and the mechanism of action involved in the TLR4/MyD88/NF-κB signaling pathway. Experimental results in vivo further suggested that the administration of POL-P3b-treated antigen-primed DC achieved remarkable tumor growth inhibition through inducing apoptosis and enhancing immune responses. Moreover, the POL-P3b-treated DC vaccine was able to inhibit lung metastases. The results proved the feasibility of POL-P3b as an edible adjuvant of the DC vaccine for anti-breast cancer therapy.

摘要

先前的研究报告表明,马齿苋多糖(POL-P3b)是一种免疫调节剂。然而,关于 POL-P3b 作为一种新型免疫佐剂与树突状细胞(DC)疫苗联合用于乳腺癌治疗的研究甚少。在这项工作中,制备了负载小鼠 4T1 肿瘤细胞抗原的 DC 疫苗,以评估 POL-P3b 诱导源自小鼠骨髓的 DC 成熟和功能的特性,然后研究 DC 疫苗联合 POL-P3b 对体内和体外乳腺癌的影响。使用扫描电子显微镜观察 DC 的形态变化。通过流式细胞术和同种异体淋巴细胞反应检测 DC 的表型和功能。通过 ELISA 检测 DC 培养上清液中的细胞因子水平。通过 Western blot 分析检测 TLR4、MyD88 和 NF-κB 的蛋白表达。通过 TUNEL 染色和免疫组织化学分别分析肿瘤组织的凋亡检测和蛋白表达。通过检测血液学和血液生化指标以及组织病理学分析评估 POL-P3b 的安全性。POL-P3b 可以诱导 DC 活化和成熟,这归因于增强了特异性抗肿瘤免疫反应,作用机制涉及 TLR4/MyD88/NF-κB 信号通路。体内实验结果进一步表明,POL-P3b 处理的抗原致敏 DC 通过诱导细胞凋亡和增强免疫反应来实现显著的肿瘤生长抑制。此外,POL-P3b 处理的 DC 疫苗能够抑制肺转移。这些结果证明了 POL-P3b 作为 DC 疫苗抗乳腺癌治疗的可食用佐剂的可行性。

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