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Use of CoCl#-[2] in preparation of drug for treating leukemia

A technology of leukemia and medicine, applied in the field of application of CoCl2 in the preparation of medicines for treating leukemia

Inactive Publication Date: 2006-02-22
SHANGHAI SECOND MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Although the current research on hypoxia and HIF-1α involves many fields, so far, there is no research report on its role in leukemia differentiation and how to use hypoxia and HIF-1α-related signaling pathways to induce differentiation and treat leukemia

Method used

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  • Use of CoCl#-[2] in preparation of drug for treating leukemia
  • Use of CoCl#-[2] in preparation of drug for treating leukemia
  • Use of CoCl#-[2] in preparation of drug for treating leukemia

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Experimental program
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Effect test

Embodiment 3

[0130] To understand HIF-1α and CoCl 2 Whether the differentiation of induced leukemia cells is related, the present invention uses semi-quantitative RT-PCR technology and Western blot technology to detect CoCl 2 Possible effects on the expression levels of HIF-1α mRNA and protein in cells ( Picture 10 ). The results show that 50μM CoCl 2 The treatment did not change the HIF-1α mRNA levels of all three AML cell lines tested, but it could rapidly increase the HIF-1α protein levels in NB4 and U937 cells. Therefore, like most organizations, CoCl 2 It is helpful for these two cells to stabilize the HIF-1α protein level. It is worth mentioning that HL60 cells also have the expression of HIF-1α at the mRNA level and the normal HIF-1α cDNA sequence, but CoCl 2 It does not induce stable expression of HIF-1α protein in HL60 cells.

[0131] 10. Inhibition of HIF-1α protein level will significantly antagonize CoCl 2 Inducing differentiation effect---

Embodiment 4

[0133] To further clarify whether HIF-1α is involved in CoCl 2 In the differentiation process of induced leukemia cells, the use of inhibitors of this protein to observe its effect on cell induction is a common method in current biological research. According to reports in the literature, certain nitric oxide donors, such as 3-morpholinosychnonimine (SIN-1), can reduce the stability of HIF-1α expression. Therefore, we observed that under the premise of reduced expression of HIF-1α protein, its effect on CoCl 2 The influence of induced differentiation effect ( Picture 11 ). The results showed that 500μM SIN-1 almost completely inhibited the accumulation of HIF-1α in NB4 and U937 cells. At the same time, SIN-1 can effectively antagonize CoCl while inhibiting the growth of NB4 and U937 cells. 2 The induced cell differentiation, therefore, it can be known that HIF-1α mediates or participates in the differentiation process of leukemia cells induced by hypoxia.

[0134] Through the for...

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Abstract

The present invention relates to an application of CoCl2 in preparation of medicine in treating leucosis. The common low oxygen environment analog compound can effectively inhibit degradation of HIF-1 alpha in the leucosis cell so as to induce differentiation of leucosis cell. The CoCl2 can combined with arsenic troxide (ATO) and / or all-trans-tretinoin (ATRA) to make matched application. The dose range of CoCl2 is nontoxic dose, its optimum range is 12.5-5.0 micro M. The described leucosis cell can be NB4 cell, U937 cell and Kasumi cell.

Description

Technical field [0001] The present invention relates to CoCl 2 Application in the preparation of drugs for the treatment of leukemia, the hypoxic environment simulating compound CoCl 2 Effectively inhibit HIF-1α degradation in leukemia cells, thereby inducing leukemia cells to differentiate. Background technique [0002] Leukemia is a malignant tumor of the hematopoietic system that seriously endangers human life and health. Among them, acute myeloid leukemia (AML) has received more extensive attention due to its rapid onset and high fatality rate. On the other hand, due to the convenience of obtaining materials for leukemia, and the ease of observing the efficacy, the research on the pathogenesis and therapeutics of AML has made remarkable progress in the past ten years. It is believed that future breakthroughs in tumor therapy are likely to originate from the study of leukemia first. It is known that most leukemia cells have specific cytogenetic changes, especially chromosomal ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K33/24A61K9/20A61P35/02
Inventor 陈国强黄莺赵倩
Owner SHANGHAI SECOND MEDICAL UNIV
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