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合成化学工具以提高水溶性并促进沙利霉素向癌细胞的递送。

Synthesis of chemical tools to improve water solubility and promote the delivery of salinomycin to cancer cells.

作者信息

Awad Loay

机构信息

Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.

出版信息

Exp Ther Med. 2020 Mar;19(3):1835-1843. doi: 10.3892/etm.2019.8368. Epub 2019 Dec 23.

Abstract

Chemotherapy and radiation are unable to eliminate all cancer cells, particularly apoptosis-resistant cancer cells, despite their ability to kill cancer cluster cells. Thus, it is important to identify methods that eliminate all cancer cells in order to prevent relapse. Salinomycin has the ability to control and eradicate different types of cancer, including breast cancer; however, its molecular mechanism remains unclear. The main difficulty in testing salinomycin activity and understanding the governing mechanisms is its low solubility in water (17 mg/l), which can hinder convenient delivery of salinomycin to the protein receptor at the cell surface of stem cells. In the present study, salinomycin was conjugated to the trans-activator of transcription-protein in order to facilitate its delivery to the cancer cells. Conjugated salinomycin demonstrated improved solubility in both . Salinomycin was tested in breast cancer cells (MCF7 and JIMT-1) by the cleavage of the linker through photolysis at l≥365 nm during analysis, in the present study.

摘要

化疗和放疗尽管能够杀死癌细胞团簇,但无法消除所有癌细胞,尤其是抗凋亡癌细胞。因此,识别能够消除所有癌细胞以防止复发的方法非常重要。沙利霉素有能力控制和根除包括乳腺癌在内的不同类型癌症;然而,其分子机制仍不清楚。测试沙利霉素活性和理解其调控机制的主要困难在于它在水中的溶解度低(17毫克/升),这可能会阻碍沙利霉素便捷地传递到干细胞表面的蛋白质受体。在本研究中,将沙利霉素与转录激活蛋白结合,以促进其传递到癌细胞。结合后的沙利霉素在两者中的溶解度均有所提高。在本研究的分析过程中,通过在波长≥365纳米时进行光解来切割连接子,从而在乳腺癌细胞(MCF7和JIMT-1)中对沙利霉素进行了测试。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a5c/7027072/565e1bc87215/etm-19-03-1835-g00.jpg

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