Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, 1985717443, Iran.
Department of Veterinary Pathology, Islamic Azad University, Abhar Branch, Abhar, Iran.
Eur J Nutr. 2018 Apr;57(3):1025-1044. doi: 10.1007/s00394-017-1387-1. Epub 2017 Feb 22.
Chlorella vulgaris (CV) has exhibited immune-enhancing and protective activities against cancer and infections. However, there is an increasing concern about the use of Chlorella species in human, regarding its various molecules with antigenic features found in infectious microorganisms. Our goal was to investigate the impact of higher concentrations of CV on tumor growth in spontaneous mouse mammary tumor (SMMT) models.
Balb/c mice were daily given CV powder at doses of 0, 200, or 300 mg/kg for 42 days (CONTROL, CV200, and CV300 groups, respectively; n = 6/group). On day 14, the SMMT was inoculated. Tumor volume (TV) and body weight (BW) were monitored on 5-day intervals following tumor challenge. On day 43, blood, spleen, lungs, and tumor tissues were collected. Histopathological examinations on lungs and tumor tissues were performed following hematoxylin-eosin staining. Intratumor expression of 27 genes was assessed by real-time PCR. Total IgG, IFNγ, and IL-4 levels in serum and spleen culture supernatant were measured by ELISA.
The TV/BW index showed significant increase in the CV200 group compared to the CONTROL (p = 0.047). The CV200 tumors exhibited more malignant phenotype, higher angiogenesis rate, and lower peritumoral neutrophil and macrophage-to-lymphocyte infiltration ratio compared to the CONTROL. Serum concentrations of IFNγ, IL-4, and IgG were declined, and the spleen IFNγ and IgG production was higher in the CV200 compared to the CONTROL. The IL-1β, IL-10, TGFβ1, FOXP3, HO-1, Gr1, CD11b, PCNA, LCN2, iNOS2, VEGFR2, CD31, and CD105L expressions were markedly increased in the CV200 tumors compared to the CONTROL (p = 0.001, 0.002, 0.006, 0.021, 0.004, 0.030, 0.016, 0.031, 0.025, 0.008, 0.014, 0.022, and 0.037, respectively). The changes in cytokine, IgG and gene expression values considerably correlated with tumor size, as well as with each other.
Our data provided evidence that C. vulgaris at a specific dose (200 mg/kg) promoted tumor growth in a mammary tumor model. This consequence might reflect an immune derangement in favor of developing a protumor microenvironment. However, this hypothesis needs to be further investigated in future.
小球藻（CV）具有增强免疫和预防癌症和感染的作用。然而，人们越来越关注小球藻属在人类中的应用，因为其在感染性微生物中发现的各种具有抗原特征的分子。我们的目标是研究较高浓度的 CV 对自发性乳腺肿瘤（SMMT）模型中肿瘤生长的影响。
Balb/c 小鼠每天给予 CV 粉末，剂量分别为 0、200 或 300mg/kg，持续 42 天（分别为对照组、CV200 组和 CV300 组，每组 6 只）。在第 14 天接种 SMMT。在肿瘤接种后每 5 天监测肿瘤体积（TV）和体重（BW）。在第 43 天，收集血液、脾脏、肺和肿瘤组织。苏木精-伊红染色后对肺和肿瘤组织进行组织病理学检查。通过实时 PCR 评估肿瘤内 27 个基因的表达。通过 ELISA 测量血清和脾培养上清液中的总 IgG、IFNγ和 IL-4 水平。
CV200 组的 TV/BW 指数与对照组相比显著增加（p=0.047）。与对照组相比，CV200 肿瘤表现出更高的恶性表型、更高的血管生成率以及更低的肿瘤周围中性粒细胞和巨噬细胞向淋巴细胞浸润比率。CV200 组血清 IFNγ、IL-4 和 IgG 浓度下降，脾 IFNγ和 IgG 产生高于对照组。与对照组相比，CV200 肿瘤中的 IL-1β、IL-10、TGFβ1、FOXP3、HO-1、Gr1、CD11b、PCNA、LCN2、iNOS2、VEGFR2、CD31 和 CD105L 表达明显增加（p=0.001、0.002、0.006、0.021、0.004、0.030、0.016、0.031、0.025、0.008、0.014、0.022 和 0.037）。细胞因子、IgG 和基因表达值的变化与肿瘤大小以及彼此之间密切相关。
我们的数据提供了证据表明，CV 在特定剂量（200mg/kg）下促进了乳腺肿瘤模型中的肿瘤生长。这种后果可能反映了有利于形成促肿瘤微环境的免疫失调。然而，这一假设需要在未来进一步研究。
