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葡甘露聚糖作为膳食补充剂在小鼠模型中治疗乳腺癌的研究

Glucomannan as a Dietary Supplement for Treatment of Breast Cancer in a Mouse Model.

作者信息

Ahmadi Nioosha, Jahantigh Hamid Reza, Noorbazargan Hassan, Yazdi Mohammad Hossein, Mahdavi Mehdi

机构信息

Advanced Therapy Medicinal Product (ATMP) Department, Breast Cancer Research Center, Motamed Cancer Institute, Academic Center for Education, Culture and Research (ACECR), Tehran 1999614414, Iran.

Department of Microbiology and Virology, School of Medicine, Kerman University of Medical Sciences, Kerman 7616913555, Iran.

出版信息

Vaccines (Basel). 2022 Oct 19;10(10):1746. doi: 10.3390/vaccines10101746.

DOI:10.3390/vaccines10101746
PMID:36298611
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9608331/
Abstract

Konjac glucomannan (KGM) is a water-soluble polysaccharide derived from the Amorphophallus's tuber and, as herbal medicine has shown, can suppress tumor growth or improve health. However, there has been no investigation into the effects of KGM on breast tumor-bearing mice. Therefore, in two cohort experiments, we assessed the effect of glucomannan at daily doses of 2 and 4 mg for 28 days as a dietary supplement and also glucomannan in combination with tumor lysate vaccine as an adjuvant. Tumor volume was monitored twice weekly. In addition, TNF-α cytokines and granzyme B (Gr-B) release were measured with ELISA kits, and IL-2, IL-4, IL-17, and IFN-γ were used as an index for cytotoxic T lymphocyte activity. Moreover, TGF-β and Foxp3 gene expression were assessed in a real-time PCR test. The results show that glucomannan as a dietary supplement increased the IFN-γ cytokine and Th1 responses to suppress tumor growth. Glucomannan as a dietary supplement at the 4 mg dose increased the IL-4 cytokine response compared to control groups. In addition, cell lysate immunization with 2 or 4 mg of glucomannan suppressed tumor growth. As an adjuvant, glucomannan at both doses showed 41.53% and 52.10% tumor suppression compared with the PBS group. Furthermore, the administration of glucomannan as a dietary supplement or adjuvant reduced regulatory T cell response through decreasing TGF-β and Foxp3 gene expression in the tumor microenvironment. In conclusion, glucomannan as a dietary supplement or adjuvant enhanced the immune responses of tumor-bearing mice and decreased immune response suppression in the tumor milieu, making it a potentially excellent therapeutic agent for lowering breast tumor growth.

摘要

魔芋葡甘聚糖(KGM)是一种从魔芋块茎中提取的水溶性多糖,如草药研究所示,它可以抑制肿瘤生长或改善健康状况。然而,尚未有人研究KGM对荷乳腺肿瘤小鼠的影响。因此,在两项队列实验中,我们评估了葡甘聚糖作为膳食补充剂,以每日2毫克和4毫克的剂量连续服用28天的效果,同时也评估了葡甘聚糖与肿瘤裂解物疫苗联合作为佐剂的效果。每周对肿瘤体积进行两次监测。此外,使用酶联免疫吸附测定试剂盒测量肿瘤坏死因子-α(TNF-α)细胞因子和颗粒酶B(Gr-B)的释放,并将白细胞介素-2(IL-2)、白细胞介素-4(IL-4)、白细胞介素-17(IL-17)和干扰素-γ(IFN-γ)作为细胞毒性T淋巴细胞活性的指标。此外,通过实时聚合酶链反应测试评估转化生长因子-β(TGF-β)和叉头框蛋白3(Foxp3)基因的表达。结果表明,作为膳食补充剂的葡甘聚糖增加了IFN-γ细胞因子和Th1反应,从而抑制肿瘤生长。与对照组相比,4毫克剂量的葡甘聚糖作为膳食补充剂增加了IL-4细胞因子反应。此外,用2毫克或4毫克葡甘聚糖进行细胞裂解物免疫可抑制肿瘤生长。作为佐剂,与磷酸盐缓冲盐水(PBS)组相比,两种剂量的葡甘聚糖均显示出41.53%和52.10%的肿瘤抑制率。此外,作为膳食补充剂或佐剂使用葡甘聚糖,可通过降低肿瘤微环境中TGF-β和Foxp3基因的表达来减少调节性T细胞反应。总之,葡甘聚糖作为膳食补充剂或佐剂可增强荷瘤小鼠的免疫反应,并减少肿瘤微环境中的免疫反应抑制,使其成为降低乳腺肿瘤生长的潜在优秀治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f033/9608331/1d39979fda88/vaccines-10-01746-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f033/9608331/dff07a983238/vaccines-10-01746-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f033/9608331/87047fa56ab9/vaccines-10-01746-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f033/9608331/f3ab86ac95eb/vaccines-10-01746-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f033/9608331/35f71c6a0596/vaccines-10-01746-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f033/9608331/2eda86fa1a4a/vaccines-10-01746-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f033/9608331/1d39979fda88/vaccines-10-01746-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f033/9608331/dff07a983238/vaccines-10-01746-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f033/9608331/87047fa56ab9/vaccines-10-01746-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f033/9608331/f3ab86ac95eb/vaccines-10-01746-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f033/9608331/35f71c6a0596/vaccines-10-01746-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f033/9608331/2eda86fa1a4a/vaccines-10-01746-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f033/9608331/1d39979fda88/vaccines-10-01746-g006.jpg

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