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Composition of albendazole and multiple myeloma clinical medicine and application

A multiple myeloma, albendazole technology, applied in the field of medicine, to achieve a strong inhibitory effect

Pending Publication Date: 2021-08-10
CENT SOUTH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The role of albendazole in MM and BTZ resistance has not been reported

Method used

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  • Composition of albendazole and multiple myeloma clinical medicine and application
  • Composition of albendazole and multiple myeloma clinical medicine and application
  • Composition of albendazole and multiple myeloma clinical medicine and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] In this embodiment, albendazole of different concentrations is used to treat ANBL6-BR cells, and the survival rate is detected by manual counting. The influence of ANBL6-BR cell clone formation ability, the experimental steps are as follows:

[0027] 1. ANBL6-BR comes from the Institute of Hematology, Chinese Academy of Medical Sciences, and is a MM cell resistant to BTZ. The sensitivity of ANBL6-BR cells to BTZ was detected by manual counting; ANBL6-BR cells were treated with different concentrations of albendazole, and the effect of albendazole on the survival rate of ANBL6-BR cells was calculated by manual counting;

[0028] ① Collect the ANBL6-BR cells in the logarithmic growth phase, resuspend in Sijiqing 1640 medium (Gibco) containing 20% ​​FBS (fetal bovine serum, Sijiqing) in mass concentration, add to 96-well plate, make each well 1× 10 4 cells, the volume of each well is 100 μL;

[0029] ②A total of 8 groups were set up, which were the control group with dr...

Embodiment 2

[0039] In this example, the method of cell counting was used to detect the synergistic effect of albendazole and BTZ combined with different concentration ratios on ANBL6-BR cells. The experimental steps are as follows:

[0040] 1. Collect ANBL6-BR cells in the logarithmic growth phase, adjust the concentration of the cell suspension, add to a 96-well plate, 100 μL per well, 1×10 4 cells;

[0041]2. Set up the control group that adds drug solvent (1640 medium that contains volume concentration 0.1% DMSO as drug solvent), experimental group adds independent ABZ (0.05 μ M, 0.1 μ M, 0.2 μ M), independent BTZ (10nM, 20nM , 40nM) and ABZ combined with BTZ (0.05μM+20nM, 0.05μM+40nM, 0.1μM+10nM, 0.1μM+20nM, 0.1μM+40nM, 0.2μM+10nM, 0.2μM+20nM, 0.2μM+40nM) , 15 groups in total, set 3-5 replicate wells for each concentration, and incubate in a cell culture incubator for 48 hours;

[0042] 3. Mix the cells in the well plate, mix the cell suspension with the mass concentration of 0.4% ...

Embodiment 3

[0045] In this example, flow cytometry was used to detect ALDH1 after albendazole and BTZ alone or in combination treated MM cells resistant to BTZ + Changes in cell proportions. Aldehyde dehydrogenases (ALDHs) are detoxifying enzymes highly expressed in various cancer stem cells (CSCs) including multiple myeloma stem-like cells (MMSCs). ALDH1 + MM cells represent a part of MMSCs, or from a certain point of view, represent a more extensively differentiated proliferating progenitor cell population, which has stem cell characteristics. Detection of ALDH1 + The ALDEFLUOR kit of cell number ratio was purchased from Stem Cell Technologies, and the ALDH1 + For the detection of cells, PI is propidium iodide, which is a nucleic acid dye.

[0046] 1. Flow cytometry detection of ALDH1 in ANBL6-BR cells treated with albendazole and BTZ alone or in combination + Changes in cell ratio;

[0047] ① Collect ANBL6-BR cells in the logarithmic growth phase, adjust the concentration of the ...

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Abstract

The invention discloses a composition of albendazole and multiple myeloma clinical drugs and application of the composition. Multiple myeloma drug-resistant cells are treated with albendazole, and it is found that albendazole has a remarkable inhibition effect on ANBL6-BR cells and can inhibit the cloning number of the ANBL6-BR cells in vitro. A series of experiments prove that albendazole has a relatively strong inhibition effect on bortezomib drug-resistant cells, and can realize sensitization on bortezomib in multiple myeloma bortezomib drug-resistant cells; the albendazole and bortezomib composition has a stronger inhibition effect on multiple myeloma cells and multiple myeloma stem cell-like cells. Albendazole is expected to be used as an auxiliary drug of bortezomib to play a role in drug-resistant and difficult-to-treat multiple myeloma.

Description

technical field [0001] The invention relates to a medicine for treating multiple myeloma, in particular to the composition and application of albendazole and clinical medicine for multiple myeloma. It belongs to the field of medical technology. Background technique [0002] Multiple myeloma (multiple myeloma, MM) is a malignant plasma cell, its incidence rate ranks second among all hematological malignancies, and it is characterized by malignant proliferation of clonal plasma cells, which can lead to a series of clinical symptoms, including anemia, Hypercalcemia, renal failure and bone lesions. In the past few years, proteasome inhibitors and immunomodulatory drugs have made remarkable progress in the treatment of MM, however, almost all patients still maintain resistance and eventually relapse, and MM is still incurable. [0003] Bortezomib (BTZ), which can inhibit the 26S proteasome, is currently the main chemotherapy drug for MM. BTZ can exert effects on multiple pathwa...

Claims

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Application Information

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IPC IPC(8): A61K31/4184A61K38/05A61K45/06A61P35/00A61P7/00
CPCA61K31/4184A61K38/05A61K45/06A61P35/00A61P7/00A61K2300/00
Inventor 萧小鹃刘静易慧梁龙王彦鹏
Owner CENT SOUTH UNIV