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application of Largozole in preparation of drug for treating diseases caused by Msi1 gene ectopic overexpression

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

Active Publication Date: 2020-02-07
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 Largozole in preparation of drug for treating diseases caused by Msi1 gene ectopic overexpression
  • application of Largozole in preparation of drug for treating diseases caused by Msi1 gene ectopic overexpression
  • application of Largozole in preparation of drug for treating diseases caused by Msi1 gene ectopic overexpression

Examples

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Embodiment 1

[0039] Example 1 Application of Largozole in the treatment of Paget disease outside the breast caused by overexpression of Msi1 gene

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

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

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

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

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Abstract

The invention discloses an application of Largozole in preparation of a drug for treating diseases caused by Msi1 gene ectopic overexpression. The invention confirms for the first time that the Largozole can inhibit expression of Msi1 gene, and after DTG mice are smeared with the Largozole drug, expression of the Msi1 in a transcription level and a translation level is reduced. Through histological observation and immunohistochemical staining, the invention finds that the symptom of the mouse extramammary Paget disease is well recovered, and the invention indicates that the Largozole can relieve the symptom of the mouse extramammary Paget disease by reducing expression of the Msi1. The invention provides the new drug for treating the extramammary Paget disease of mice and people.

Description

Technical field [0001] The invention relates to the field of biomedicine, in particular to the application of Largozole in the preparation of medicines for treating diseases caused by the ectopic overexpression of Msi1 gene. Background technique [0002] Largozole was originally discovered by the team of Dr. Luesch from the University of Florida and isolated from cyanobacteria with sixteen-membered cyclic peptide lactone compounds. It is an inhibitor of histone deacetylase. Found in human and murine cells, the drug has good antiproliferative activity. The drug acts on different cells in a dose-dependent manner. At high concentrations, it has an inhibitory effect on the growth of human breast tumor epithelial cells (MDA-MB-231), and is not sensitive to non-cancerous murine epithelial cells (NMuMG). Many natural anti-tumor drugs are not so selective for cells. In addition, it has a good inhibitory effect on human neuroblastoma cells (IMR-32) and colon tumor cells (HT29) (Ying Y,...

Claims

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Application Information

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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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