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Use of MG132 in preparing medicine for synergistic inductive differentiation therapy of leukaemia

A technology of MG132 and induction of differentiation, applied in drug combinations, dipeptide components, anti-tumor drugs, etc.

Inactive Publication Date: 2011-04-06
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

At present, many literatures have reported that MG132 can induce the apoptosis of various tumor cells and is a potential anti-tumor drug. Solving related drug resistance issues has not yet been reported

Method used

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  • Use of MG132 in preparing medicine for synergistic inductive differentiation therapy of leukaemia
  • Use of MG132 in preparing medicine for synergistic inductive differentiation therapy of leukaemia
  • Use of MG132 in preparing medicine for synergistic inductive differentiation therapy of leukaemia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] With different concentrations of MG132 (1×10 -8 -1×10 -6 M) with retinoic acid (1×10 -6 M) Combined treatment of HL60 cell lines, counting the number of living cells by the trypan blue exclusion method and drawing the growth curve of HL60 cells at 24, 48, 72, 96, and 120 hours after the treatment, and found that low concentrations of MG132 (1 × 10 -8 -1×10 -7 M) Single use has no obvious inhibitory effect on the growth of HL60 cells, but it can significantly promote the growth inhibitory effect of retinoic acid on HL60 cells, and it is time-dose dependent. For the results, see figure 1 .

Embodiment 2

[0020] MG132 (1×10 -7 M) with retinoic acid (1×10 -9 -1×10 -5 M) Treat the HL60 cell line together, and count the number of living cells by the placenta blue exclusion method after 120 hours. It is found that MG132 can promote different concentrations of retinoic acid (1 × 10 -9 -1×10 -5 M) growth inhibitory effect on HL60 cells, see results figure 2 .

Embodiment 3

[0022] Using different concentrations of MG132 (1×10 -8 -1×10 -6 M) with retinoic acid (1×10 -6 M) Combined treatment of HL60 cell line, the cells were collected 72 hours after the treatment, and the changes of the cell cycle were detected. Cells were fixed overnight with ice-cold 70% ethanol, centrifuged to discard the fixative before going to the machine, resuspended the cells with PBS, and added 500 μl of propidium iodide (PI) staining solution (containing 50 μg / ml PI, 100 μg / ml RNase A ), stained at room temperature for 30 min in the dark. The DNA content was measured by flow cytometry, and the cell cycle percentage was calculated by ModFIT software. The results showed that MG132 could significantly promote retinoic acid-induced cell G0 / G1 phase arrest in a dose-dependent manner, while MG132 had no significant effect on the cell cycle. See results image 3 .

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Abstract

The invention provides the application of the compound MG132 in preparing the drug to synergistically promote the retinoic acid drug for the differentiation induction therapy of leukemia. The molecular formula of the compound MG132 is C26H41N3O5, the concentration of the compound MG132 is 1*10<-8> to 1*10<-6>M, and the concentration of the retinoic acid is 1*10<-9> to 1*10<-5>M. The compound MG132 with the single effect can not induce the leukemia cells to be differentiated, but promote the differentiation induction effect of the retinoic acid drug on the leukemia cells, which is presented as the promotion of the anti-proliferative effect and the cell cycle arresting effect of the retinoic acid drug on the leukemia cells, promote the expression of the differentiation specific antigen CD11b on the leukemia cell surface, and increasing the number of segmented cells. The invention opens up the new drug application field of the compound MG132.

Description

technical field [0001] The invention belongs to the pharmaceutical application of compounds, and relates to the application of compound MG132 and retinoic acid drugs in the preparation of combined treatment of leukemia drugs, especially the application of compound MG132 in the preparation of synergistically promoting retinoic acid drugs to induce differentiation and treatment of leukemia. Background technique [0002] Since Sachs first proposed the concept of differentiation therapy in the 1970s, the significance of abnormal cell differentiation in the pathogenesis and therapeutics of malignant tumors has aroused widespread interest and has become one of the hotspots in current oncology research. one. Tumor cells are similar to undifferentiated embryonic cells in terms of shape, function, metabolism, and behavior. Therefore, chemical drugs are used to induce tumor cell differentiation and reverse their malignant phenotypes such as proliferation, invasion, and metastasis, mak...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/05A61K31/203A61P35/02
Inventor 何俏军杨波方艳芬应美丹罗沛华朱狄峰
Owner ZHEJIANG UNIV
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