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

A technology for leukemia and leukemia cells, used in drug combinations, anti-tumor drugs, pill delivery, etc.

Inactive Publication Date: 2004-08-25
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

[0135] In order to understand HIF-1α and CoCl 2 Whether there is a connection between the differentiation of induced leukemia cells, 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 ( Figure 10 ). The results showed that 50 μM CoCl 2 Treatment did not alter HIF-1α mRNA levels in all three AML cell lines examined, but it rapidly increased HIF-1α protein levels in NB4 and U937 cells. Therefore, like most organizations, CoCl 2 It is beneficial for these two kinds of cells to stabilize the HIF-1α protein level. It is worth mentioning that HL60 cells also express HIF-1α and normal HIF-1α cDNA sequence at the mRNA level, but CoCl 2 However, it did not induce the stable expression of HIF-1α protein in HL60 cells.

[0136] 10. Inhibition of HIF-1α protein level will significantly antagonize CoCl 2 Differentiation-inducing effect ---

Embodiment 4

[0138] In order to further clarify whether HIF-1α is involved in CoCl 2 Inducing the differentiation process of leukemia cells, using the inhibitor of this protein to observe its influence on cell induction effect is a common method in current biological research. According to literature reports, 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 effect of inducing differentiation effect ( Figure 11 ). The results showed that 500 μM SIN-1 almost completely inhibited the aggregation of HIF-1α in NB4 and U937 cells. Meanwhile, SIN-1 effectively antagonized CoCl while inhibiting the growth of NB4 and U937 cells 2 Therefore, it can be seen that HIF-1α mediates or participates in the process of hypoxia-induced leukemia cell differentiation.

[0139] Through the aforementioned experiments and analysis...

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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 medicines for treating leukemia, hypoxic environment simulating compound CoCl 2 Effectively inhibit the degradation of HIF-1α in leukemia cells, thereby inducing the differentiation of leukemia cells. 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 attention due to its rapid onset and high mortality. On the other hand, due to the convenience of obtaining leukemia materials and observing the curative effect, the research on the pathogenesis and treatment of AML has made remarkable progress in the past ten years. It is believed that future breakthroughs in cancer therapy may first come from research on leukemia. Specific cytogenetic changes, especially chromosomal translocations, are known to be present in most leukemia cells. These...

Claims

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Application Information

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