蜂胶通过影响肿瘤微环境中的上皮分化和肠道免疫对早期结直肠癌具有抗癌作用。

Propolis Has an Anticancer Effect on Early Stage Colorectal Cancer by Affecting Epithelial Differentiation and Gut Immunity in the Tumor Microenvironment.

机构信息

Department of Surgery, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei City 243089, Taiwan.

School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242062, Taiwan.

出版信息

Nutrients. 2023 Oct 24;15(21):4494. doi: 10.3390/nu15214494.

Abstract

Colorectal cancer (CRC) is one of the most common cancers and is the second leading cause of cancer-related death in the world. Due to the westernization of diets, young patients with CRC are often diagnosed at advanced stages with an associated poor prognosis. Improved lifestyle choices are one way to minimize CRC risk. Among diet choices is the inclusion of bee propolis, long recognized as a health supplement with anticancer activities. Understanding the effect of propolis on the gut environment is worth exploring, and especially its associated intratumoral immune changes and its anticancer effect on the occurrence and development of CRC. In this study, early stage CRC was induced with 1,2-dimethylhydrazine (DMH) and dextran sulfate sodium (DSS) for one month in an animal model, without and with propolis administration. The phenotypes of early stage CRC were evaluated by X-ray microcomputed tomography and histologic examination. The gut immunity of the tumor microenvironment was assessed by immunohistochemical staining for tumor-infiltrating lymphocytes (TILs) and further comparative quantification. We found that the characteristics of the CRC mice, including the body weight, tumor loading, and tumor dimensions, were significantly changed due to propolis administration. With further propolis administration, the CRC tissues of DMH/DSS-treated mice showed decreased cytokeratin 20 levels, a marker for intestinal epithelium differentiation. Additionally, the signal intensity and density of CD3 and CD4 TILs were significantly increased and fewer forkhead box protein P3 (FOXP3) lymphocytes were observed in the lamina propria. In conclusion, we found that propolis, a natural supplement, potentially prevented CRC progression by increasing CD3 and CD4 TILs and reducing FOXP3 lymphocytes in the tumor microenvironment of early stage CRC. Our study could suggest a promising role for propolis in complementary medicine as a food supplement to decrease or prevent CRC progression.

摘要

结直肠癌(CRC)是最常见的癌症之一,也是世界上癌症相关死亡的第二大主要原因。由于饮食的西化,患有 CRC 的年轻患者经常被诊断为晚期,预后较差。改善生活方式是降低 CRC 风险的一种方法。在饮食选择中,包括被长期认为具有抗癌活性的蜂用蜂胶。了解蜂胶对肠道环境的影响值得探索,特别是其与肿瘤内免疫变化的关联及其对 CRC 发生和发展的抗癌作用。在这项研究中,我们在动物模型中用 1,2-二甲基肼(DMH)和葡聚糖硫酸钠(DSS)诱导早期 CRC 一个月,同时给予和不给予蜂胶。通过 X 射线微计算机断层扫描和组织学检查评估早期 CRC 的表型。通过肿瘤浸润淋巴细胞(TILs)的免疫组织化学染色和进一步的比较定量评估肿瘤微环境的肠道免疫。我们发现,由于蜂胶的给予,CRC 小鼠的特征,包括体重、肿瘤负荷和肿瘤尺寸,发生了显著变化。随着进一步的蜂胶给药,DMH/DSS 处理的 CRC 组织显示出细胞角蛋白 20 水平降低,这是肠上皮分化的标志物。此外,CD3 和 CD4 TILs 的信号强度和密度显著增加,固有层中 FOXP3 淋巴细胞减少。总之,我们发现天然补充剂蜂胶可能通过增加 CD3 和 CD4 TILs并减少肿瘤微环境中的 FOXP3 淋巴细胞来预防 CRC 的进展。我们的研究可能表明蜂胶作为一种补充剂在补充医学中具有降低或预防 CRC 进展的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0e2/10648826/207c3be82658/nutrients-15-04494-g001.jpg

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