水飞蓟素抑制结直肠癌细胞的增殖和 PD-L1 表达,并增加肿瘤小鼠体内的 CD8+ 炎症细胞数量

IF 2.6 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY
Maysoon Al-Haideri
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引用次数: 0

摘要

简介水飞蓟素作为一种中草药,对肿瘤细胞有抗癌作用,而对正常细胞毒性较低。本研究在体外和体内评估了水飞蓟素对结直肠癌细胞增殖和凋亡的影响及其对癌细胞免疫反应的影响:方法和材料:水飞蓟素对CT-26和Caco-2细胞增殖和凋亡的影响通过MTT试验和PI染色来证实。方法:水飞蓟素对 CT-26 和 Caco-2 细胞增殖和凋亡的影响通过 MTT 试验和 PI 染色法进行了验证。对血液样本和肿瘤组织进行 qRT-PCR 分析。脾脏组织用于评估 CD8+ T 细胞免疫反应。对肿瘤组织进行了组织学研究:结果:水飞蓟素对 CT-26 和 Caco-2 细胞有抗增殖作用。在水飞蓟素的作用下,两种细胞系的免疫原性细胞死亡标志物(钙网素暴露、ATP分泌和HMGB1分泌)均显著增加。与细胞增殖有关的基因,尤其是β-Catenin和Cycline D1,以及抗凋亡基因(如Bcl-2)的表达在水飞蓟素治疗的小鼠中明显减少,而促凋亡基因Bax的表达则有所增加。水飞蓟素暴露的肿瘤组织中 PD-L1 的 RNA 水平下降。此外,与未接受水飞蓟素治疗的小鼠相比,接受水飞蓟素治疗的小鼠脾脏中 CTLs 的数量有所增加。组织学分析显示,水飞蓟素治疗小鼠的肿瘤体积缩小,结直肠癌细胞的存活率也有所降低:结论:水飞蓟素对结直肠癌细胞的抑制作用几乎与多柔比星相同。我们的研究表明,植物提取的水飞蓟素具有毒性低、成本效益高、原料易得等特点,是进一步研究治疗 CRC 的良好候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Silymarin suppresses proliferation and PD-L1 expression in colorectal cancer cells and increases inflammatory CD8+ cells in tumor-bearing mice

Introduction

Silymarin as an herbal medicine has shown anticancer effects on tumor cells, while having low toxicity in normal cells. In this study, the effects of Silymarin on proliferation and apoptosis of colorectal cancer cells and its impact on immune response against cancer cells were evaluated in vitro and in vivo.

Methods and materials

The effect of Silymarin on CT-26 and Caco-2 cells proliferation and apoptosis were demonstrated by MTT assay and PI staining. A subcutaneous tumor of colorectal cancer was developed. Silymarin and Doxorubicin were administrated by intravenous injection. qRT-PCR analyses was performed on blood samples and tumor tissues. Spleen tissue was used to evaluate CD8+ T cell immune responses. Histological study was carried out on tumor tissues.

Results

Silymarin showed anti-proliferative effects on CT-26 and Caco-2 cells. The markers of immunogenic cell death (Calreticulin exposure, ATP secretion, and HMGB1 secretion) significantly increased in both cell lines in the presence of silymarin. The expression of genes related to cell proliferation particularly β-Catenin and Cycline D1, and also anti-apoptotic ones such as Bcl-2 significantly reduced in mice treated with Silymarin while the expression of pro-apoptotic Bax increased. The RNA level of PD-L1 decreased in tumor tissues exposed by Silymarin. Moreover, the number of CTLs increased in the spleen of mice treated with Silymarin in comparison with untreated mice. Decreased tumor size and also survival of colorectal cancer cells in Silymarin-treated mice were observed in histological analysis.

Conclusion

Silymarin treatment showed a suppressive role on colorectal cancer cells almost as much as Doxorubicin. Our study indicated that having a low toxicity profile, cost-effectiveness, and availability of raw materials, plant-derived Silymarin can be a good candidate for further investigation to treat CRC.

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来源期刊
CiteScore
4.30
自引率
3.70%
发文量
198
审稿时长
42 days
期刊介绍: Clinics and Research in Hepatology and Gastroenterology publishes high-quality original research papers in the field of hepatology and gastroenterology. The editors put the accent on rapid communication of new research and clinical developments and so called "hot topic" issues. Following a clear Editorial line, besides original articles and case reports, each issue features editorials, commentaries and reviews. The journal encourages research and discussion between all those involved in the specialty on an international level. All articles are peer reviewed by international experts, the articles in press are online and indexed in the international databases (Current Contents, Pubmed, Scopus, Science Direct). Clinics and Research in Hepatology and Gastroenterology is a subscription journal (with optional open access), which allows you to publish your research without any cost to you (unless you proactively chose the open access option). Your article will be available to all researchers around the globe whose institution has a subscription to the journal.
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