摘要
背景:葡萄膜黑色素瘤是成人眼内最常见的恶性肿瘤。到目前为止,还没有有效的靶向治疗药物对葡萄膜黑色素瘤患者。青蒿琥酯是从中药青蒿中提取的一种半合成的青蒿素衍生物,用于治疗严重的多重耐药疟疾。青蒿琥酯除了具有抗疟作用外,由于其对多种癌症的Wnt/β-catenin通路的抑制作用,被认为是一种抗癌药物。然而,青蒿琥酯对葡萄膜黑色素瘤的作用尚不清楚。目的:评价青蒿琥酯对葡萄膜黑色素瘤细胞的抗肿瘤作用,并从Wnt/β-catenin通路、细胞生长、细胞死亡、细胞迁移、侵袭性和癌干细胞特性等方面进行分析。方法:应用原代(92.1,Mel270)和转移性(Omm 1和Omm2.3)葡萄膜黑色素瘤细胞。免疫荧光染色、双荧光素酶报告试验、Western blotting、MTS、软琼脂克隆技术、Annexin V/PI分析、伤口愈合划痕试验、体外跨孔迁移和侵袭试验、醛脱氢酶(ALDH)分析和黑色素瘤形成试验等。都完成了。结果:青蒿琥酯可抑制GSK 3β在S9的磷酸化,降低β-catenin及其下游靶点(c-Myc,cyclinD 1)的蛋白水平。青蒿琥酯能有效抑制细胞活力和集落形成能力。青蒿琥酯明显诱导细胞凋亡。此外,青蒿琥酯对葡萄膜黑色素瘤细胞的迁移和侵袭有明显的抑制作用,对体外培养的CSCs具有明显的损伤作用。结论:青蒿琥酯对葡萄膜黑色素瘤有潜在的治疗作用。
关键词: 青蒿琥酯,癌症干细胞样移位,侵袭,葡萄膜黑色素瘤,Wnt /β-连环蛋白。
Current Cancer Drug Targets
Title:The Anti-malarial Drug Artesunate Blocks Wnt/β-catenin Pathway and Inhibits Growth, Migration and Invasion of Uveal Melanoma Cells
Volume: 18 Issue: 10
关键词: 青蒿琥酯,癌症干细胞样移位,侵袭,葡萄膜黑色素瘤,Wnt /β-连环蛋白。
摘要: Background: Uveal melanoma is the most common primary intraocular malignancy in adults. So far, there have been no effective targeted therapeutic agents in patients with uveal melanoma. Artesunate is a semi-synthetic derivative of artemisinin extracted from traditional Chinese medicine Artemisia annua L for treatment of severe and multidrug-resistant malaria. Besides its antimalarial activity, artesunate is identified as an anti-cancer drug due to the inhibition of Wnt/β- catenin pathway in multiple types of cancer. However, the effect of artesunate on uveal melanoma remains unknown.
Objective: We evaluated the anti-tumor effects of artesunate on uveal melanoma cells, and analyzed in terms of Wnt/β-catenin pathway, cell growth, cell death, cell migration, invasion and cancer stemlike cells (CSCs) properties.
Methods: Primary (92.1, Mel270) and metastatic (Omm1 and Omm2.3) uveal melanoma cells were used. Immunofluorescence staining, dual luciferase reporter assay, Western blotting, MTS, soft agar cloning technique, Annexin V/PI analyses, wound healing scratch assay, in vitro transwell migration and invasion assays, aldehyde dehydrogenase (ALDH) analyses and melanosphere formation assay et al. were carried out.
Results: Artesunate suppressed the phosphorylation of GSK3β at S9, and lowered the protein level of β-catenin and its downstream targets (c-Myc, cyclin D1). Artesunate potently inhibited cell viability and colony formation ability. Treatment with artesunate significantly induced apoptosis. In addition, artesunate significantly reduced the migration and invasion of uveal melanoma cells, impaired the traits of CSCs in vitro.
Conclusion: Artesunate may be a potential interest for the therapy of uveal melanoma.
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Cite this article as:
The Anti-malarial Drug Artesunate Blocks Wnt/β-catenin Pathway and Inhibits Growth, Migration and Invasion of Uveal Melanoma Cells, Current Cancer Drug Targets 2018; 18 (10) . https://dx.doi.org/10.2174/1568009618666180425142653
DOI https://dx.doi.org/10.2174/1568009618666180425142653 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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