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特林通过抑制恶性黑素瘤细胞中血管生成素表达发挥抗肿瘤活性。

Terrein Exhibits Anti-tumor Activity by Suppressing Angiogenin Expression in Malignant Melanoma Cells.

机构信息

Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.

Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science, Gifu, Japan.

出版信息

Cancer Genomics Proteomics. 2024 Sep-Oct;21(5):464-473. doi: 10.21873/cgp.20464.

DOI:10.21873/cgp.20464
PMID:39191499
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11363929/
Abstract

BACKGROUND/AIM: Malignant melanoma is a tumor with a poor prognosis that can metastasize distally at an early stage. Terrein, a metabolite produced by Aspergillus terreus, suppresses the expression of angiogenin, an angiogenic factor. However, the pharmacological effects of natural terrein have not been elucidated, because only a small amount of terrein can be extracted from large fungal cultures. In this study, we investigated the antineoplastic effects of terrein on human malignant melanoma cells and its underlying mechanisms.

MATERIALS AND METHODS

Human malignant melanoma cell lines were cultured in the presence of terrein and analyzed. Angiogenin production was evaluated using ELISA. Ribosome biosynthesis was evaluated using silver staining of the nucleolar organizer region. Intracellular signaling pathways were analyzed using western blotting. Malignant melanoma cells were transplanted subcutaneously into the backs of nude mice. The tumors were removed at 5 weeks and analyzed histopathologically.

RESULTS

Terrein inhibited angiogenin expression, proliferation, migration, invasion, and ribosome biosynthesis in malignant melanoma cells. Terrein was shown to inhibit tumor growth and angiogenesis in animal models.

CONCLUSION

This study demonstrated that terrein has anti-tumor effects against malignant melanoma. Furthermore, chemically synthesized non-natural terrein can be mass-produced and serve as a novel potential anti-tumor drug candidate.

摘要

背景/目的:恶性黑色素瘤是一种预后不良的肿瘤,早期即可远处转移。土霉素是土曲霉产生的一种代谢产物,能抑制血管生成因子血管生成素的表达。然而,由于从大量真菌培养物中只能提取到少量土霉素,因此其药理学作用尚未阐明。本研究旨在探讨土霉素对人恶性黑素瘤细胞的抗肿瘤作用及其作用机制。

材料和方法

用土霉素培养人恶性黑素瘤细胞系并进行分析。用 ELISA 法评估血管生成素的产生。用核仁组成区银染法评估核糖体生物合成。用 Western blot 法分析细胞内信号通路。将恶性黑素瘤细胞皮下移植到裸鼠背部。5 周后切除肿瘤并进行组织病理学分析。

结果

土霉素抑制恶性黑素瘤细胞中的血管生成素表达、增殖、迁移、侵袭和核糖体生物合成。土霉素在动物模型中显示出抑制肿瘤生长和血管生成的作用。

结论

本研究表明土霉素对恶性黑色素瘤具有抗肿瘤作用。此外,化学合成的非天然土霉素可以大量生产,并可能成为一种新型的潜在抗肿瘤药物候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0374/11363929/006e1bdcb8a5/cgp-21-471-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0374/11363929/17285a539e4c/cgp-21-465-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0374/11363929/0145b321cd43/cgp-21-466-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0374/11363929/793c285602f4/cgp-21-469-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0374/11363929/6c292f9869bc/cgp-21-470-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0374/11363929/a311f9c1be55/cgp-21-471-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0374/11363929/006e1bdcb8a5/cgp-21-471-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0374/11363929/17285a539e4c/cgp-21-465-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0374/11363929/0145b321cd43/cgp-21-466-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0374/11363929/793c285602f4/cgp-21-469-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0374/11363929/6c292f9869bc/cgp-21-470-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0374/11363929/a311f9c1be55/cgp-21-471-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0374/11363929/006e1bdcb8a5/cgp-21-471-g0002.jpg

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