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丹皮酚作为顺铂的增效剂诱导 4T1 乳腺癌细胞体外和体内死亡的新亮点。

A New Highlight of Decne Properties as Potential Adjuvant in Combination with Cisplatin to Induce Cell Death of 4T1 Breast Cancer Cells In Vitro and In Vivo.

机构信息

Research Unit Bioactive Natural Products and Biotechnology UR17ES49, Faculty of Dental Medicine of Monastir, University of Monastir, Avicenne street, 5000 Monastir, Tunisia.

Université de Bourgogne Franche-Comté, F-21000 Dijon, France.

出版信息

Cells. 2020 Feb 4;9(2):362. doi: 10.3390/cells9020362.

DOI:10.3390/cells9020362
PMID:32033130
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7072491/
Abstract

Despite major advances in the last 10 years, whether in terms of prevention or treatment, the 5 year survival rate remains relatively low for a large number of cancers. These therapeutic failures can be the consequence of several factors associated with the cellular modifications or with the host by itself, especially for some anticancer drugs such as cisplatin, which induces a nephrotoxicity. In the strategy of research for active molecules capable both of exerting a protective action against the deleterious effects of cisplatin and exerting a chemosensitizing action with regard to cancer cells, we tested the potential effects of Ephedra alata Decne extract (E.A.) rich in polyphenolic compounds towards a 4T1 breast cancer model in vitro and in vivo. We showed that E.A. extract inhibited cell viability of 4T1 breast cancer cells and induced apoptosis in a caspase-dependent manner, which involved intrinsic pathways. Very interestingly, we observed a synergic antiproliferative and pro-apoptotic action with cisplatin. These events were associated with a strong decrease of breast tumor growth in mice treated with an E.A./cisplatin combination and simultaneously with a decrease of hepato- and nephrotoxicities of cisplatin.

摘要

尽管在过去的 10 年中取得了重大进展,无论是在预防还是治疗方面,许多癌症的 5 年生存率仍然相对较低。这些治疗失败可能是与细胞修饰或宿主本身相关的几个因素的结果,特别是对于某些抗癌药物,如顺铂,它会引起肾毒性。在研究既能发挥保护作用对抗顺铂的有害作用,又能对癌细胞发挥化疗增敏作用的活性分子的策略中,我们测试了富含多酚类化合物的麻黄提取物(E.A.)对体外和体内 4T1 乳腺癌模型的潜在影响。我们表明,E.A.提取物抑制了 4T1 乳腺癌细胞的活力,并以依赖半胱天冬酶的方式诱导细胞凋亡,这涉及内在途径。非常有趣的是,我们观察到与顺铂具有协同的抗增殖和促凋亡作用。这些事件与用 E.A./顺铂联合治疗的小鼠中的乳腺肿瘤生长强烈减少以及顺铂的肝毒性和肾毒性同时减少有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92d3/7072491/c1b2263620ee/cells-09-00362-g008.jpg
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