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Application of AZA (Azelaic Acid) in preparation of AML (Acute Myeloid Leukemia) resistant and chemosensitization drugs

An acute myeloid, azelaic acid technology, applied in the direction of anhydride/acid/halide active ingredients, antineoplastic drugs, drug combinations, etc.

Active Publication Date: 2017-04-26
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, its role in acute myeloid leukemia has not been reported

Method used

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  • Application of AZA (Azelaic Acid) in preparation of AML (Acute Myeloid Leukemia) resistant and chemosensitization drugs
  • Application of AZA (Azelaic Acid) in preparation of AML (Acute Myeloid Leukemia) resistant and chemosensitization drugs
  • Application of AZA (Azelaic Acid) in preparation of AML (Acute Myeloid Leukemia) resistant and chemosensitization drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] [Example 1] MMT method to detect the killing effect of azelaic acid on various AML cell lines

[0029] Plant U937, THP-1, MOLM-13, U937, THP-1, MOLM-13, KG-1 cells on the 96-well plate, each 100 μL 6×10 4 Each cell / mL was added with 10 μL of 0, 1.25, 2.5, 5, and 10 mM AZA, and MTT was added 24, 48, and 72 hours after drug treatment, and the absorbance at 570 nm was detected.

[0030] Such as figure 1 As shown, AZA can inhibit the viability of these cells in a dose- and time-dependent manner.

Embodiment 2

[0031] [Example 2] Soft agarose colony formation experiment

[0032] Plant AML cells (U937, THP-1, MOLM-13, U937, THP-1, MOLM-13, KG-1) on a six-well plate, first pour 2ml of medium containing 0.7% agar into the six-well plate , when the agar is solidified, add 1ml of 0.35% agar medium containing 5000 cells to each well, replace 3ml of fresh medium with the specified AZA concentration each time, and count the samples with remaining cells > 50 after 14 days of incubation.

[0033] Such as figure 2 As shown in A, AZA can inhibit the clonal proliferation of these AML cells.

Embodiment 3

[0034] [Example 3] Flow cytometric detection of the effect of AZA on apoptosis of AML cells

[0035] Will 1×10 5 -1×10 7 Put the cells into a 1.5ml EP tube and centrifuge at 3000r / min for 5min, discard the supernatant, add PBS100μL to suspend the cells, add Annexin-V / PI staining, incubate at 4°C for 45min, and collect and resuspend all the cells in 24h after AZA treatment In 100ml of buffer solution, it was detected by flow cytometry that AZA could induce the apoptosis of AML cells, such as figure 2 Shown in B.

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Abstract

The invention discloses application of AZA (Anchoic Acid) in preparation of acute myelogenous leukemia (AML) resistant and chemosensitization drugs. Through demonstration, AZA has a killing effect on multiple AML cell strains (U937, THP-1, KG-1, NB4, and HL-60), and can be used for inhibiting the proliferation of AML cells and simultaneously inducing cell apoptosis, and can be combined with Arac in use to promote the killing effect of Arac on the AML cells. AZA does not have any toxic and side effects, and the price can be accepted by most patients; and AZA can be combined with chemotherapeutics, namely Arac in use to promote the killing effect of Arac on the AML cells, and also to reduce the dosage of Arac to alleviate the toxic and side effects caused by chemotherapy, so that a new approach and method is provided for treatment and curing of the AML.

Description

technical field [0001] The invention belongs to the field of antitumor drugs, in particular to the application of azelaic acid in the preparation of anti-acute myeloid leukemia and chemotherapy sensitization drugs. Background technique [0002] Acute myeloid leukemia (AML) is the most common malignant tumor of the blood system and belongs to a class of clonal malignant diseases of hematopoietic system tissues. The induction regimen for acute myeloid leukemia is always based on anthracycline antibiotics combined with standard doses of cytarabine (Arac). Toxic and side effects such as bone marrow suppression, gastrointestinal toxicity, and cardiotoxicity may occur after chemotherapy. In addition, there is also chemotherapy resistance. Our previous research found that the overall antioxidant capacity (T-AOC) decreased in patients with AML relapse, the level of ROS in the body increased significantly, and 8-OHdG, a recognized marker of oxidative DNA damage, also increased signif...

Claims

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Application Information

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IPC IPC(8): A61K31/20A61K31/7068A61P35/02
CPCA61K31/20A61K31/7068A61K2300/00
Inventor 周芙玲潘运宝金艳霞丁路刘盼
Owner WUHAN UNIV
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