Application of largazole in preparation of medicine for treating diseases caused by ectopic overexpression of msi1 gene

A technology of overexpression and disease, applied in the field of biomedicine, can solve problems such as no good treatment methods

Active Publication Date: 2022-06-24
CHINA AGRI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] At present, there is no good treatment method at home and abroad for the treatment of Paget's disease outside the mammary gland. Once it is diagnosed, it needs to be treated by surgical resection.

Method used

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  • Application of largazole in preparation of medicine for treating diseases caused by ectopic overexpression of msi1 gene
  • Application of largazole in preparation of medicine for treating diseases caused by ectopic overexpression of msi1 gene
  • Application of largazole in preparation of medicine for treating diseases caused by ectopic overexpression of msi1 gene

Examples

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Effect test

Embodiment 1

[0039] Example 1 Application of Largazole in the treatment of extramammary Paget disease caused by Msi1 gene overexpression

[0040] (1) Preparation of extramammary mouse model of paget disease (inducible mouse model)

[0041] In this example, a transgenic mouse model (DTG mouse) in which the expression of Musashi1 is controlled by Doxycyline (Dox) was prepared. The overexpression of the foreign gene Musashi1 was induced by feeding Dox to mice. 48h after Musashi1 overexpression (ie, 48h after Dox administration), the symptoms of initial extramammary paget's disease can appear.

[0042] The specific preparation method of DTG mice is as follows:

[0043] K14rtta transgenic mice were mated with TRE-Msi1 transgenic mice (for the construction methods of the two transgenic mice, see Wang S, Li N, Yousefi M, Nakauka-Ddamba A, Li F, Parada K, et al. (2015) Transformation of the intestinal epithelium by the MSI2 RNA-binding protein. Nat Commun 6:6517) to produce offspring mice, when...

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Abstract

The invention discloses the application of Largazole in the preparation of medicines for treating diseases caused by ectopic overexpression of Msi1 gene. The present invention proves for the first time that Largazole can inhibit the expression of Msi1 gene. After smearing DTG mice with Largazole drug, the expression of Msi1 at the transcriptional level and the translational level are all reduced. Through histological observation and immunohistochemical staining, it is found that the Paget The symptoms of the disease were well recovered, indicating that Largazole slowed down the symptoms of Paget's disease outside the mammary glands in mice, which was achieved by reducing the expression of Msi1. The invention provides a new drug for treating the extramammary Paget's disease of mice and humans.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to the application of Largazole in preparing a medicine for treating diseases caused by ectopic overexpression of Msi1 gene. Background technique [0002] Largazole was originally discovered by Dr. Luesch's team at the University of Florida, USA, and isolated from cyanobacteria with a sixteen-membered cyclic peptide lactone compound. Inhibitors of histone deacetylases. The drug has good antiproliferative activity found in human and murine cells. The drug acts on different cells in a dose-dependent manner, inhibits the growth of human breast tumor epithelial cells (MDA-MB-231) at high concentrations, and is insensitive to noncancerous murine epithelial cells (NMuMG). Many natural antitumor drugs are not so selective for cells. In addition, it also has a good inhibitory effect on human neuroblastoma cells (IMR-32) and colon tumor cells (HT29) (Ying Y, 2008, J AmChem Soc, 30:8455-8459). ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/429A61P15/14A61P17/00
CPCA61K31/429A61P15/14A61P17/00
Inventor 于政权宋永利毕雪云
Owner CHINA AGRI UNIV
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