Application of matrine to preparation of medicament for treating CML

A technology for chronic myeloid and leukemia, applied in the fields of medicinal chemistry and cell biology

Active Publication Date: 2015-02-25
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, there is no report about the application of matrine in the preparation of CML drugs with T315I mutation

Method used

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  • Application of matrine to preparation of medicament for treating CML
  • Application of matrine to preparation of medicament for treating CML
  • Application of matrine to preparation of medicament for treating CML

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Example 1: Matrine inhibits the proliferation of CML cell lines and induces their apoptosis.

[0023] CML cell lines K562 (introduced from the Shanghai Cell Bank of the Chinese Academy of Sciences), K562 / G (gifted by Tianjin Blood Institute, China), 32Dp210, 32Dp210-T315I (gifted by Harbin Institute of Hematology) were selected as the research objects. Take K562, K562 / G, 32Dp210, 32Dp210-T315I in the logarithmic growth phase, wash once with RPMI 1640, add PMI 1640 medium containing 10% fetal bovine serum by volume fraction, inoculate in 96-well plate, adjust the cell concentration to 0.5- 1×10 5 / ml, the total volume of each well was 200μl, and were treated with 0, 0.2, 0.4, 0.8, 1.6, 3.2mM matrine, respectively. After 24 hours, add 20 μl of 5mg / ml MTT working solution to each well, mix well and incubate in a 37°C, 5% CO2 saturated humidity incubator for 4-6 hours. 2000 rpm, 5min, carefully absorb the supernatant with a pipette, add 200ml DMSO to each well, and bl...

Embodiment 2

[0025] Example 2: Effects of matrine on growth inhibition and apoptosis induction of CML primary cells and normal bone marrow cells.

[0026] Collect 2-5ml of bone marrow or peripheral blood from patients with new-onset CML and normal people, centrifuge with lymphocyte separation medium density gradient at 2000rpm for 20min, absorb mononuclear cells, and wash 3 times with 1×PBS. Seed in 96-well plate, adjust the cell concentration to 5×10 5 / ml, the total volume of each well was 200μl, treated with 0, 0.2, 0.4, 0.8, 1.6, 3.2mM matrine respectively; inoculated in a 6-well plate, adjusted the cell concentration to 5×10 5 / ml, the final volume was 5ml, and they were treated with 0, 0.4, 0.8, 1.6mM matrine, respectively. After 24 hours, the growth inhibitory effect was detected by MTT method, and the cell apoptosis was detected by Annexin V / PI double staining flow cytometry. All experiments were repeated three times. see results image 3 and Figure 4 , showing that matrine h...

Embodiment 3

[0027] Example 3: Matrine enhances the sensitivity of K562 to imatinib.

[0028] Take K562 and 32Dp210-T315I in the logarithmic growth phase, seed them in 96-well plates, and adjust the cell concentration to 5×10 5 / ml, the total volume of each well is 200μl, and they are treated with 0.4uM imatinib, 0.8mM matrine alone and in combination. After 24 hours, growth inhibition was detected by MTT assay. All experiments were repeated three times. see results Figure 5 , showing that matrine significantly enhanced the sensitivity of K562 to imatinib, matrine single-drug group and combination group, imatinib single-drug group and combination group had statistical differences (p0.05).

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Abstract

The invention provides application of matrine to preparation of a medicament for treating CML (chronic myelogenous leukemia), and particularly application to preparation of a medicament for treating T315I mutated CML. Researches show that the matrine has an obvious concentration-dependent apoptosis inducing effect on K562 and 32Dp210-T315I; the matrine has obvious concentration-dependent growth inhibiting and apoptosis inducing effects on CML primary cells; for normal bone marrow cells, the matrine has a low toxic effect, and can obviously concentration-dependently reduce expression of c-Myc of K562 and 32Dp210-T315I. The matrine provided by the invention has low toxicity and has tumor targeting. The invention provides the theoretical basis for searching a new therapeutic target of CML and a matrine target and enabling the matrine to enter clinical application as a medicament.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry and cell biology, and relates to the application of matrine in the preparation of medicines for treating chronic myeloid leukemia. technical background [0002] Chronic myeloid leukemia (CML) is a malignant myeloproliferative disorder that occurs on early multipotent hematopoietic stem cells, mainly involving the myeloid lineage. Ph chromosome appears in the primary cells of about 95% of CML patients, and the banding analysis is t (9;22) (q34;q11). The Bcr / Abl fusion protein encoded by it has abnormally increased tyrosine kinase activity, which is The main mechanism leading to the development of CML. Imatinib is a tyrosine kinase inhibitor targeting Bcr / Abl, which can selectively block the binding site between ATP and the catalytic center of the kinase, and specifically inhibit the expression of Bcr / Abl. It is currently the first-line drug for CML patients, and it can make 75% of...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/4375A61K31/506A61P35/02
Inventor 金洁路莎莎陈健钱俊青娄引军马秋玲
Owner ZHEJIANG UNIV
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