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熊去氧胆酸在胰腺癌细胞模型中的抗癌作用。

Anticarcinogenic effects of ursodeoxycholic acid in pancreatic adenocarcinoma cell models.

作者信息

Kovács Patrik, Schwarcz Szandra, Nyerges Petra, Bíró Tímea Ingrid, Ujlaki Gyula, Bai Péter, Mikó Edit

机构信息

Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

MTA-DE Lendület Laboratory of Cellular Metabolism, University of Debrecen, Debrecen, Hungary.

出版信息

Front Cell Dev Biol. 2024 Dec 11;12:1487685. doi: 10.3389/fcell.2024.1487685. eCollection 2024.

DOI:10.3389/fcell.2024.1487685
PMID:39723238
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11668698/
Abstract

Changes to the composition of the microbiome in neoplasia, is termed oncobiosis, may affect tumor behavior through the changes to the secretion of bacterial metabolites. In this study we show, that ursodeoxycholic acid (UDCA), a bacterial metabolite, has cytostatic properties in pancreatic adenocarcinoma cell (PDAC) models. UDCA in concentrations corresponding to the human serum reference range suppressed PDAC cell proliferation. UDCA inhibited the expression of epithelial mesenchymal transition (EMT)-related markers and invasion capacity of PDAC cells. UDCA treatment increased oxidative/nitrosative stress by reducing the expression of nuclear factor, erythroid 2-like 2 (NRF2), inducing inducible nitric oxide synthase (iNOS) and nitrotyrosine levels and enhancing lipid peroxidation. Furthermore, UDCA reduced the expression of cancer stem cell markers and the proportion of cancer stem cells. Suppression of oxidative stress by antioxidants, blunted the UDCA-induced reduction in cancer stemness. Finally, we showed that UDCA induced mitochondrial oxidative metabolism. UDCA did not modulate the effectiveness of chemotherapy agents used in the chemotherapy treatment of pancreatic adenocarcinoma. The antineoplastic effects of UDCA, observed here, may contribute to the induction of cytostasis in PDAC cell models by providing a more oxidative/nitrosative environment.

摘要

肿瘤形成过程中微生物群组成的变化被称为肿瘤生物状态，这种变化可能通过细菌代谢产物分泌的改变来影响肿瘤行为。在本研究中，我们发现熊去氧胆酸（UDCA）这种细菌代谢产物在胰腺腺癌细胞（PDAC）模型中具有细胞生长抑制特性。对应于人类血清参考范围浓度的UDCA抑制了PDAC细胞的增殖。UDCA抑制了上皮间质转化（EMT）相关标志物的表达以及PDAC细胞的侵袭能力。UDCA处理通过降低核因子红细胞2样2（NRF2）的表达、诱导诱导型一氧化氮合酶（iNOS）和硝基酪氨酸水平以及增强脂质过氧化作用，增加了氧化/亚硝化应激。此外，UDCA降低了癌症干细胞标志物的表达和癌症干细胞的比例。抗氧化剂对氧化应激的抑制减弱了UDCA诱导的癌症干性降低。最后，我们表明UDCA诱导了线粒体氧化代谢。UDCA并未调节用于胰腺腺癌化疗的化疗药物的有效性。此处观察到的UDCA的抗肿瘤作用可能通过提供更具氧化/亚硝化的环境，有助于在PDAC细胞模型中诱导细胞生长停滞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa8b/11668698/ff177a28be6b/fcell-12-1487685-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa8b/11668698/d9e3c3b942c7/fcell-12-1487685-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa8b/11668698/6edeb70bf094/fcell-12-1487685-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa8b/11668698/7ad9bc8f2d7d/fcell-12-1487685-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa8b/11668698/787bb553bee0/fcell-12-1487685-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa8b/11668698/18041c74bf5e/fcell-12-1487685-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa8b/11668698/639f8b244fbd/fcell-12-1487685-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa8b/11668698/ae5db1dc2eae/fcell-12-1487685-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa8b/11668698/ff177a28be6b/fcell-12-1487685-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa8b/11668698/d9e3c3b942c7/fcell-12-1487685-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa8b/11668698/6edeb70bf094/fcell-12-1487685-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa8b/11668698/7ad9bc8f2d7d/fcell-12-1487685-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa8b/11668698/787bb553bee0/fcell-12-1487685-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa8b/11668698/18041c74bf5e/fcell-12-1487685-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa8b/11668698/639f8b244fbd/fcell-12-1487685-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa8b/11668698/ae5db1dc2eae/fcell-12-1487685-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa8b/11668698/ff177a28be6b/fcell-12-1487685-g008.jpg

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