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Application of nifuroxazide or salt thereof to treating osteosarcoma

A technology for nifurazide and osteosarcoma, applied in the field of treatment of osteosarcoma, nifurazide or its salts, can solve the problems that hinder the improvement of the curative effect of osteosarcoma, neurotoxicity, toxic and side effects of clinical application of doxorubicin, etc., to achieve The effect of good industry prospects

Inactive Publication Date: 2019-05-24
WEST CHINA HOSPITAL SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In general, doxorubicin belongs to anthracycline (Anthracycline) antineoplastic drugs, which has a broad spectrum of action and is clinically used for the treatment of leukemia, lymphoma, and osteosarcoma. During clinical application, severe myocardial toxicity can occur, which leads to the treatment of Myocardial toxicity has become the most important side effect hindering the clinical application of doxorubicin, and it is considered to be more dangerous than the common side effects of antineoplastic drugs such as myelosuppression, gastrointestinal and renal toxicity; cisplatin is currently more effective in clinical practice. It is widely used in the chemotherapy of various solid tumors such as ovarian cancer, prostate cancer, testicular cancer, and osteosarcoma, and all of them have shown certain curative effects. Although the protective measures such as hydration therapy are taken, the incidence of clinical nephrotoxicity is still as high as about 1 / 3
Similarly, methotrexate often causes adverse reactions such as bone marrow suppression, and ifosfamide also often causes adverse reactions of the digestive system, neurotoxicity, etc.
In addition to the many complications affecting the therapeutic effect of these clinical routine first-line drugs, there is another important factor hindering the improvement of the curative effect of osteosarcoma, which is multidrug resistance, which leads to uncontrollable recurrence and metastasis

Method used

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  • Application of nifuroxazide or salt thereof to treating osteosarcoma
  • Application of nifuroxazide or salt thereof to treating osteosarcoma
  • Application of nifuroxazide or salt thereof to treating osteosarcoma

Examples

Experimental program
Comparison scheme
Effect test

experiment example 1

[0025] Experimental example 1 Nifuzide inhibits cell proliferation in vitro

[0026] 1. Method

[0027] (1) Proliferation activity of osteosarcoma cells detected by MTT assay.

[0028] First, UMR106, MG63 and HEK 293T cells (3-5×10 3 / well) was plated in a 96-well plate at 100 μl / well. After 24 hours of incubation, different concentrations of nifurazide were added. The control group was a medium containing 0.1% DMSO. After adding the drug for 24 hours, 48 ​​hours, and 72 hours, 20 μl of 5 mg / ml MTT ( dark operation). Incubate at 37°C for 2-4 hours, then absorb all the medium, add 150 μl of DMSO, place on a shaker for 10 minutes until the formazan is completely dissolved, and then use a spectrum MAX M5 microplate spectrophotometer to measure the absorbance at 570nm . All results were replicated three times.

[0029] (2) The colony formation experiment of osteosarcoma cells.

[0030] First, UMR106 and MG63 cells were seeded in six-well plates at a concentration of 400-600...

experiment example 2

[0034] Experimental Example 2 Nifurazide Induces Osteosarcoma Cell Apoptosis and Its Effect on Apoptosis-related Proteins

[0035] 1. Method

[0036] (1) Hoechst33258 staining.

[0037] First, UMR106 cells (1~2×10 5 per well) into a 6-well plate with an 18mm coverslip. After incubation for 24 hours, add the drug and incubate again for 24 hours, then wash twice with cold PBS, fix with methanol for 15-30 minutes, and wash twice with PBS. Stain with Hoechst33258 according to the kit instructions, then take out the coverslip, place the cell side down on a glass slide dripped with 50% glycerol, and observe the apoptosis morphology with a fluorescence microscope (Leica, DM4000B).

[0038] (2) Apoptosis assay by flow cytometry.

[0039] First, UMR106 cells (1~2×10 5 per well) were planted in a 6-well plate. After incubation for 24 hours, add the drug and incubate for another 24 hours, collect the supernatant, then digest the cells with trypsin, centrifuge the supernatant and th...

experiment example 3

[0046] Experimental Example 3 Migration and Invasion of Osteosarcoma Cells Induced by Nifurazide

[0047] 1. Method

[0048] (1) Scratch test.

[0049] Seed the UMR106 cells in the logarithmic growth phase in 6-well plates. When the cells grow to cover 80% of the culture dish, use a 10μl gun tip to gently scratch the surface of the cell layer, then wash it with PBS, and then add Fresh media (with 2% serum) containing different concentrations of drugs. After incubation for 24 h, the number of cell migration in the scratch area was counted using a microscope (Zeiss, Germany)

[0050] (2) Cell migration experiment.

[0051] Add 100 μl of 1×10 to the upper chamber of each chamber 5 In the serum-free medium of UMR106 cells, 600 μl of medium containing 10% fetal bovine serum was added to the lower chamber. Drugs of different concentrations were added to the upper and lower chambers. After 24 hours, the non-migrated cells in the upper chamber were gently wiped off with a cotton...

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Abstract

The invention provides an antitumor medicine. Nifuroxazide and / or salt of the nifuroxazide are used as active components of the antitumor medicine, and pharmaceutically acceptable auxiliary componentsare added into the nifuroxazide and / or the salt to prepare the antitumor medicine. The invention further provides application of the nifuroxazide to preparing antitumor medicines. Preferably, tumor is osteosarcoma. The antitumor medicine and the application have the advantages that apoptosis of osteosarcoma cells can be effectively induced by the nifuroxazide and the salt of the nifuroxazide, osteosarcoma cell proliferation, migration and invasion can be inhibited by the nifuroxazide and the salt of the nifuroxazide, and obvious antitumor effects can be realized in an in-vivo manner; the nifuroxazide and / or the salt of the nifuroxazide can be used for preparing osteosarcoma medicines, and accordingly the antitumor medicine and the application have excellent industrial prospects.

Description

technical field [0001] The invention relates to the field of antineoplastic drugs, in particular to the application of nifurazide or its salt in the treatment of osteosarcoma. Background technique [0002] Osteosarcoma (OS) is a primary malignant bone tumor originating from bone mesenchymal cells, which is characterized by the direct formation of immature bone or osteoid tissue by proliferating tumor cells, and is prone to occur in children and adolescents. It is the eighth most common cancer in children and accounts for 20% of all primary bone malignancies. Osteosarcoma is highly aggressive and prone to lung metastases, and its survival rate is lower among pediatric cancers. [0003] The treatment of osteosarcoma mainly includes surgical resection and chemotherapy. The 5-year survival rate of patients with simple surgical resection without preoperative and postoperative chemotherapy is about 15-20%. Since the 1970s, the application of chemotherapy has greatly improved th...

Claims

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Application Information

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IPC IPC(8): A61K31/345A61P35/00
Inventor 罗翼巫丽娟谢永美屠重棋
Owner WEST CHINA HOSPITAL SICHUAN UNIV
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