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抗白血病抑制因子对荷乳腺癌 4T1 细胞 Balb/c 小鼠免疫系统的影响。

The effect of the anti-leukemia inhibitory factor on the immune system in the Balb/c mice bearing breast cancer induced with 4T1 cells.

机构信息

Reproductive Immunology Research Center, Shahid Sadoughi University of Medical Science, Daneshjou Boulevard., Yazd, Iran.

Department of Immunology, School of Medicine, Shahid Sadoughi University of Medical Sciences, International Campus, Yazd, Iran.

出版信息

Eur J Med Res. 2023 Jul 1;28(1):211. doi: 10.1186/s40001-023-01196-2.

Abstract

BACKGROUND

Breast cancer is one of the most common cancers. Leukemia inhibitory factor (LIF) is considered as one of the effective factors in the growth of breast cancer, and anti-leukemia inhibitory factor antibody is considered as one of the treatment options for this type of cancer.

METHODS

Mice models of breast cancer were made with 4T1 cell line and were randomly divided into four groups. The first group included the mice that received anti-LIF (Anti LIF group). The mice in the second group received anti-LIF and doxorubicin (Anti LIF & DOX). The mice in the third group received only doxorubicin (DOX). Finally, the mice in the fourth group did not receive any intervention. 22 days after tumor induction, some of the mice were killed, and their tumor tissues, lymph nodes, and spleens were separated for evaluating P53, Caspase-3, TIM-3, LAG-3, CTLA-4, and PD-1 genes expression. The percentage of regulatory T cells and level of interferon gamma (IFN-γ) and transforming growth factor-beta (TGF-β) were evaluated. The rest of the mice were kept to check the tumor size and their survival rate.

RESULTS

The proposed intervention did not have any significant effect on the tumor growth and the survival rate. However, the expression of P53 gene and Caspase-3 in the tumor tissue of the Anti LIF group had a significant enhancement. In tumor tissues and lymph nodes, the expression of T-bet, PD-1, TIM-3, and LAG-3 genes in the Anti LIF group showed a significant increase. There was no significant difference between groups in the percentage of regulatory T cells and level of IFN-γ and TGF-β.

CONCLUSIONS

The proposed interventions were able to have a direct effect on tumors, but no significant effect was observed on the immune system.

摘要

背景

乳腺癌是最常见的癌症之一。白血病抑制因子(LIF)被认为是乳腺癌生长的有效因素之一,抗白血病抑制因子抗体被认为是治疗这种癌症的选择之一。

方法

使用 4T1 细胞系制作乳腺癌小鼠模型,并将其随机分为四组。第一组包括接受抗 LIF(抗 LIF 组)的小鼠。第二组的小鼠接受抗 LIF 和多柔比星(抗 LIF & DOX)。第三组的小鼠仅接受多柔比星(DOX)。最后,第四组的小鼠未接受任何干预。肿瘤诱导 22 天后,部分小鼠被处死,分离其肿瘤组织、淋巴结和脾脏,评估 P53、Caspase-3、TIM-3、LAG-3、CTLA-4 和 PD-1 基因表达。评估调节性 T 细胞的百分比以及干扰素 γ(IFN-γ)和转化生长因子-β(TGF-β)的水平。其余的小鼠被保留以检查肿瘤大小和它们的存活率。

结果

所提出的干预措施对肿瘤生长和存活率没有任何显著影响。然而,抗 LIF 组肿瘤组织中 P53 基因和 Caspase-3 的表达有显著增强。在肿瘤组织和淋巴结中,抗 LIF 组的 T-bet、PD-1、TIM-3 和 LAG-3 基因的表达显著增加。调节性 T 细胞的百分比和 IFN-γ 和 TGF-β 的水平在各组之间没有显著差异。

结论

所提出的干预措施能够直接作用于肿瘤,但对免疫系统没有明显影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/158b/10314567/3bccc0d01e2d/40001_2023_1196_Fig1_HTML.jpg

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