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Application of Soimycin A in preparation of leukemia radiation and chemotherapy sensitizer

A radiochemotherapy and sensitizer technology, applied in the field of preparation of acute myeloid leukemia radiochemotherapy sensitizers, can solve the problems of unclear effects on AML tumor cells and the like

Active Publication Date: 2016-08-31
THE FIRST AFFILIATED HOSPITAL OF THIRD MILITARY MEDICAL UNIVERSITY OF PLA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The effect of Soimycin A on AML tumor cells is still unclear. In our research on the effect of FoxM1 gene on drug resistance (5-fluorouridine) of mouse bone marrow cells, we found that Soimycin A can improve the radiosensitivity of AML cell lines and AML Chemosensitivity of mice, this result has not been reported at home and abroad

Method used

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  • Application of Soimycin A in preparation of leukemia radiation and chemotherapy sensitizer
  • Application of Soimycin A in preparation of leukemia radiation and chemotherapy sensitizer
  • Application of Soimycin A in preparation of leukemia radiation and chemotherapy sensitizer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Example 1: Effect of 5-FU on Survival Rate of FoxM1 Knockout Mice

[0028] 1.1 Experimental method:

[0029] FoxM1 f1 / f1 Tie2Cre is a FoxM1 knockout mouse, FoxM1 f1 / f1 As a control mouse, Tie2Cre can mediate the knockout of target genes in the endothelium and hematopoietic system without the need for inducers, and the knockout can be maintained throughout the hematopoietic process. Select a certain number of FoxM1 respectively f1 / f1 Mice (11 in total) and FoxM1 f1 / f1 Tie2Cre mice (12 in total) were injected with 5-fluorouracil (150 mg / kg) intraperitoneally, and re-injected at 6 days and 16 days, and the survival rate of the mice was continuously monitored.

[0030] 1.2 Experimental results:

[0031] 5-fluorouracil is a broad-spectrum antineoplastic drug that interferes with DNA synthesis, FoxM1 after a second injection of 5-fluorouracil f1 / f1 Mice did not appear dead, FoxM1 after three injections of 5-fluorouracil f1 / f1 Mouse survival dropped slightly to 90%. wh...

Embodiment 2

[0032] Example 2: Effect of Soimycin A pretreatment on the apoptosis rate of myeloid leukemia cell lines after radiotherapy

[0033] 2.1 Experimental method:

[0034] K562 and HL-60 cell lines were inoculated respectively, pretreated with 0.5% DMSO and SoimycinA (0.5μM) for 18 hours respectively, one group of cells was treated with a total of 2Gy of radioactive rays (0.5Gy / min), and the other group of cells was statically and then continue to incubate for 12 hours. After the cells were collected, they were double-stained with Annexin V and DAPI, and analyzed by flow cytometry.

[0035] 2.2 Experimental results:

[0036] The apoptosis rate of K562 and HL-60 cells in DMSO pretreatment group increased from 7%, 8% to 31%, 41% after radiotherapy. The apoptosis rate of K562 and HL-60 cells in Soimycin A pretreatment group increased from 8% and 8% to 59% and 76% respectively after radiotherapy. It shows that Soimycin A pretreatment can significantly improve the radiosensitivity o...

Embodiment 3

[0037] Example 3: Effect of Soimycin A pretreatment on the survival rate of myeloid leukemia mice after chemotherapy

[0038] 3.1 Experimental method:

[0039] A total of 20 NSGS recipient mice were irradiated with 2.5Gy, and each recipient mouse was injected with 0.2×10 6 HL-60 cells, after 7 days, the recipient mice were divided into two groups of 10 each, and treated with 5-fluorouracil (150mg / kg), and one group was injected with DMSO twice within 24 hours before the injection of 5-fluorouracil as the control group (once every 12 hours), another group was injected with Siomycin A (30 mg / kg, once every 12 hours) twice through the tail vein, and the survival rate of the mice was continuously monitored.

[0040] 3.2 Experimental results:

[0041] The AML mice constructed by HL-60 cell transplantation were pretreated with DMSO before receiving 5-fluorouracil treatment. The mice began to die sharply at 23 days, and all died at 32 days. Death occurred, and some mice survived a...

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Abstract

The invention relates to application of Soimycin A in preparation of an acute myeloid leukemia (AML) radiation and chemotherapy sensitizer. According to the application, in vitro and animal experiments show that the Soimycin A has an effect of improving the radiosensitivity of an AML cell line HL-60 and a chromicmyeloid leukemia (CML) cell line K562, and prove that the Soimycin A has an effect of improving the survival rate of AML mice constructed by HL-60 cell transplantation after chemotherapy. The sensitizer disclosed by the invention has a good application prospect for AML radiation and chemotherapy.

Description

technical field [0001] The present invention relates to the application of Soimycin A in the preparation of radiochemotherapy sensitizer for acute myeloid leukemia Background technique [0002] Acute myeloid leukemia (AML) is the most common type of malignant clonal disease in leukemia. AML mainly manifests as abnormal proliferation, differentiation disorder and apoptosis arrest of hematopoietic stem cells, stagnant in various stages of immature maturity, and Extensive invasion of bone marrow and other organs and tissues. At present, the treatment of acute myeloid leukemia is mainly chemotherapy, supplemented by radiotherapy. Chemotherapy drugs mainly inhibit the rapid proliferation and division of tumor cells by interfering with DNA synthesis; radiotherapy generates a large amount of energy through ionizing radiation, thereby destroying the chromosome structure of tumor cells and stopping cell growth. Despite the continuous emergence of new chemotherapy drugs and continuo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4709A61K41/00A61P35/02
CPCA61K31/4709A61K41/0038
Inventor 侯宇陈哲黎雯
Owner THE FIRST AFFILIATED HOSPITAL OF THIRD MILITARY MEDICAL UNIVERSITY OF PLA
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