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兔源抗菌肽衍生物对 MDA-MB-231 乳腺癌细胞系的细胞毒性作用及作用机制研究。

Investigation of cytotoxic effect and action mechanism of a synthetic peptide derivative of rabbit cathelicidin against MDA-MB-231 breast cancer cell line.

机构信息

Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran.

Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran.

出版信息

Sci Rep. 2024 Jun 12;14(1):13497. doi: 10.1038/s41598-024-64400-1.

DOI:10.1038/s41598-024-64400-1
PMID:38866982
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11169400/
Abstract

Antimicrobial peptides (AMPs) have sparked significant interest as potential anti-cancer agents, thereby becoming a focal point in pursuing novel cancer-fighting strategies. These peptides possess distinctive properties, underscoring the importance of developing more potent and selectively targeted versions with diverse mechanisms of action against human cancer cells. Such advancements would offer notable advantages compared to existing cancer therapies. This research aimed to examine the toxicity and selectivity of the nrCap18 peptide in both cancer and normal cell lines. Furthermore, the rate of cellular death was assessed using apoptosis and acridine orange/ethidium bromide (AO/EB) double staining at three distinct incubation times. Additionally, the impact of this peptide on the cancer cell cycle and migration was evaluated, and ultimately, the expression of cyclin-dependent kinase 4/6 (CDK4/6) genes was investigated. The results obtained from the study demonstrated significant toxicity and selectivity in cancer cells compared to normal cells. Moreover, a strong progressive increase in cell death was observed over time. Furthermore, the peptide exhibited the ability to halt the progression of cancer cells in the G1 phase of the cell cycle and impede their migration by suppressing the expression of CDK4/6 genes.

摘要

抗菌肽 (AMPs) 作为潜在的抗癌药物引起了极大的关注,因此成为寻求新型抗癌策略的焦点。这些肽具有独特的特性,强调开发更有效和选择性靶向、具有不同作用机制的版本的重要性,以对抗人类癌细胞。与现有的癌症治疗方法相比,这些进展将具有显著的优势。本研究旨在研究 nrCap18 肽在癌细胞和正常细胞系中的毒性和选择性。此外,还通过在三个不同的孵育时间使用凋亡和吖啶橙/溴化乙锭 (AO/EB) 双重染色来评估细胞死亡的速度。此外,还评估了该肽对癌细胞周期和迁移的影响,并最终研究了细胞周期蛋白依赖性激酶 4/6 (CDK4/6) 基因的表达。研究结果表明,与正常细胞相比,该肽在癌细胞中表现出显著的毒性和选择性。此外,随着时间的推移,细胞死亡呈强烈的递增趋势。此外,该肽能够阻止癌细胞在细胞周期的 G1 期进展,并通过抑制 CDK4/6 基因的表达来抑制其迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/893a/11169400/ae7c0dc67785/41598_2024_64400_Fig9_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/893a/11169400/3a7df532f25c/41598_2024_64400_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/893a/11169400/908ce6a8d448/41598_2024_64400_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/893a/11169400/85643fb537d1/41598_2024_64400_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/893a/11169400/c6de21ff1e31/41598_2024_64400_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/893a/11169400/60c3543209ba/41598_2024_64400_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/893a/11169400/ae7c0dc67785/41598_2024_64400_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/893a/11169400/e9d7b2527d8d/41598_2024_64400_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/893a/11169400/7966880a10ea/41598_2024_64400_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/893a/11169400/c666f173d299/41598_2024_64400_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/893a/11169400/3a7df532f25c/41598_2024_64400_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/893a/11169400/908ce6a8d448/41598_2024_64400_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/893a/11169400/85643fb537d1/41598_2024_64400_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/893a/11169400/c6de21ff1e31/41598_2024_64400_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/893a/11169400/60c3543209ba/41598_2024_64400_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/893a/11169400/ae7c0dc67785/41598_2024_64400_Fig9_HTML.jpg

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