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Cryptotanshinone pharmaceutical composition and application thereof in preparation of CML (chronic myeloid leukemia) treatment drug

A technology of chronic granulocytes and cryptotanshinone, which is applied in the field of medicine and biology, can solve the problems of no research report on molecular mechanism and no related report on treatment effect, so as to reduce toxic side effects and treatment costs, improve chemotherapy sensitivity, and improve sensitivity sexual effect

Inactive Publication Date: 2018-01-16
ZHEJIANG CHINESE MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the effect of cryptotanshinone on chronic myeloid leukemia in vivo and in vitro has not yet been systematically studied. The effect of cryptotanshinone on patients with drug-resistant chronic myeloid leukemia has not yet been clarified. The therapeutic effect of cryptotanshinone combined with tyrosine kinase inhibitors has not been seen. Related reports, the molecular mechanism of its action has not been reported

Method used

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  • Cryptotanshinone pharmaceutical composition and application thereof in preparation of CML (chronic myeloid leukemia) treatment drug
  • Cryptotanshinone pharmaceutical composition and application thereof in preparation of CML (chronic myeloid leukemia) treatment drug
  • Cryptotanshinone pharmaceutical composition and application thereof in preparation of CML (chronic myeloid leukemia) treatment drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Study on anti-leukemia effect of cryptotanshinone combined with tyrosine kinase inhibitors imatinib, nilotinib and dasatinib

[0035] Cell culture: The human chronic myeloid leukemia cell line K562 was purchased from the Shanghai Institute of Cell Biology, Chinese Academy of Sciences. The multidrug-resistant strain K562 / ADM was independently established by the limiting gradient dilution method, and its resistance to imatinib was More than 20, and the resistance to nilotinib and dasatinib was more than 15. K562 and K562 / ADM cells were cultured in RPIM 1640 medium containing 10% fetal bovine serum, 100 U / ml penicillin and 100 μg / ml streptomycin at 37°C, 5% CO 2 Subculture in the incubator and change the medium every two days.

[0036] Drug mother solution preparation:

[0037] Cryptotanshinone was prepared into 10mM working mother solution with DMSO, stored at -20°C for later use, and adjusted to the required concentration with RPIM1640 culture medium before use. Imati...

Embodiment 2

[0064] Molecular Mechanism of Cryptotanshinone Synergizing with Imatinib in Anti-leukemia

[0065] In order to further clarify the application prospects of cryptotanshinone in the treatment of leukemia, the present invention studies the mechanism of action of cryptotanshinone in improving the sensitivity of imatinib chemotherapy, and detects the Bcr-abl closely related to leukemia apoptosis after cryptotanshinone treatment. Changes in the activity of signaling pathways.

[0066] Take the leukemia cells K562 in the logarithmic growth phase and the multidrug-resistant strain K562 / ADM cells, and adjust the cell density to 5×10 5 After inoculation at 2 mL per well in a 6-well plate and culturing overnight, the medium containing different concentrations of cryptotanshinone (5 μM, 10 μM, 15 μM and 20 μM) was added for 24 hours, and the control group (Control) was added with fresh culture medium. Among them, the concentration of cryptotanshinone mother solution is 10 mM, prepared wi...

Embodiment 3

[0074] Effect of cryptotanshinone combined with imatinib on apoptosis of leukemia cells

[0075] In order to further clarify the anti-leukemia effect of cryptotanshinone combined with tyrosine kinase inhibitors, the present invention detected the effect of cryptotanshinone combined with imatinib on the apoptosis rate of leukemia cells K562 and multi-drug resistant strain K562 / ADM cells.

[0076] The experiment of cell apoptosis rate was detected by Annexin V-FITC / PI double staining method. Take K562 and K562 / ADM cells in the logarithmic growth phase, adjust the cell suspension density to 5×10 5 cells / ml, and then inoculated in 60mm diameter petri dish with 5ml. Add no drug (Control), 10 μM cryptotanshinone (10 μM CPT), 0.5 μM imatinib (0.5 μM imatinib), 10 μM cryptotanshinone and 0.5 μM imatinib in K562 cells Fresh culture medium (imatinib+CPT) of K562 / ADM cells, were added without drug (Control), containing 10μM cryptotanshinone (10μM CPT), containing 2μM imatinib (2μM imat...

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Abstract

The invention discloses cryptotanshinone pharmaceutical composition and an application thereof in preparation of a CML (chronic myeloid leukemia) treatment drug. The cryptotanshinone pharmaceutical composition contains cryptotanshinone and a tyrosine kinase inhibitor, with the adoption of cryptotanshinone for treatment, protein expression level of Bcr-Abl genes in CML K562 and multi-drug resistantstrains K562 / ADM cells can be remarkably reduced, cell proliferation inhibition ratio of the tyrosine kinase inhibitor is increased, and apoptosis rate of CML K562 cells and K562 / ADM cells can be remarkably increased through combination of cryptotanshinone and the tyrosine kinase inhibitor. With the adoption of the cryptotanshinone pharmaceutical composition, chemosensitivity of tyrosine kinase can be improved, chemotherapy drug dosage of a patient is reduced, toxic and side effects on a human body are reduced, and a new treatment scheme is provided for clinical treatment of CML.

Description

technical field [0001] The invention belongs to the field of medicine and biology, and in particular relates to a cryptotanshinone pharmaceutical composition and its application in the preparation of medicines for treating chronic myelogenous leukemia. Background technique [0002] Chronic myeloid leukemia (CML) is a malignant tumor originating from pluripotent hematopoietic stem cells. Its main genetic feature is the occurrence of chromosomal translocation to form the Philadelphia chromosome, which then encodes the Bcr-Abl fusion protein. The protein has high tyrosine kinase activity and plays an important regulatory function in the course of CML. The incidence of CML in my country accounts for more than 15% of newly diagnosed leukemia in adults. It is characterized by accelerated and uncontrolled growth of myeloid cells and excessive accumulation of myeloid cells in the blood. [0003] The advent of tyrosine kinase inhibitors (TKI) has brought a revolutionary change in th...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K31/506A61K31/58A61P35/02
Inventor 程汝滨葛宇清张光霁朱玲燕
Owner ZHEJIANG CHINESE MEDICAL UNIVERSITY
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