Use of nitazoxanide and pharmaceutically acceptable salt thereof in preparation of drug for treating bladder cancers

A technology for nitazoxanide and bladder cancer, which is applied in the new medical field of nitazoxanide, can solve the problems of poor curative effect, large toxic and side effects, and achieves inhibition of dryness maintenance, inhibition of bladder tumor growth, good treatment and application prospects Effect

Inactive Publication Date: 2020-11-24
SHENZHEN LUOHU PEOPLELS HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] In view of the above-mentioned deficiencies in the prior art, the purpose of the present invention is to provide nitazoxanide and its pharmaceutically acceptable salts in the preparation of medicines for the treatment of bladder cancer, aiming to solve the poor curative effect and toxicity of existing medicines for the treatment of bladder cancer. big side effects

Method used

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  • Use of nitazoxanide and pharmaceutically acceptable salt thereof in preparation of drug for treating bladder cancers
  • Use of nitazoxanide and pharmaceutically acceptable salt thereof in preparation of drug for treating bladder cancers
  • Use of nitazoxanide and pharmaceutically acceptable salt thereof in preparation of drug for treating bladder cancers

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Detection of the killing effect of nitazoxanide on bladder cancer cells

[0035] 1) Bladder tumor cell culture in vitro: Bladder cancer cells used in this experiment mainly include UMUC-3, T24, 5637, and MGHU3 cells, among which UMUC-3 and T24 cells were treated with DMEM containing 10% fetal bovine serum and 1% double antibody Culture medium, 5637 and MGHU3 cells use RPMI1640 culture medium containing 10% fetal bovine serum and 1% double antibody, all at 37°C, 5% CO 2 cultured in an incubator. When the cells grow to 80% density, trypsinize, collect the cells by centrifugation and resuspend in the culture medium, take an appropriate amount of cell suspension for passage.

[0036] 2) In vitro proliferation inhibition experiment: take a certain number of cells (0.6×10 4 Each well) was inoculated in a 96-well plate, and a control group and an experimental group were set up, with 6 replicate wells in each group. After 12 hours of culture, the above-mentioned bladder tumor...

Embodiment 2

[0041] Detection of the damage of nitazoxanide to the mitochondria of bladder cancer cells

[0042] 1), JC-1 staining to detect changes in cell membrane potential (MMP): take a certain number of cells (4×10 5 / well) inoculated in 6-well plates, set up control and experimental groups, treated MGHU3 cells with 60 μM concentration of nitazoxanide after 12 hours of culture, continued to culture for 6, 12, and 24 hours; digested and collected cells and washed them with pre-cooled PBS, using a concentration of Cells were resuspended in 5 μM JC-1 solution (PBS configuration), and stained at 37°C for 15 minutes in the dark; after filtering through a 300-mesh sieve, the changes of mitochondrial membrane potential MMP were detected by Guava easyCyte flow cytometer (JC-1 was Polymer state: Ex=488nm, Em=575nm, JC-1 is monomeric state: Ex=488nm, Em=525nm). The data were analyzed using FlowJo software, and the results were as follows: image 3 shown.

[0043] The change of mitochondrial ...

Embodiment 3

[0047] Detection of Bladder Cancer Cell Apoptosis Induced by Nitazoxanide

[0048] 1), Annexin V-FITC / PI double staining method to detect cell apoptosis: take a certain number of cells (4 × 10 5 Each well) was inoculated in a 6-well plate, and the control group and the experimental group were set up. After 12 hours of culture, the MGHU3 cells were treated with different concentrations of nitazoxanide, and the culture continued for 48 hours; The cells were resuspended with 3 μL of PI in PBS solution (500 μL), and stained at 37°C for 15 minutes in the dark; after filtering through a 300-mesh sieve, the cell apoptosis was detected with a Guava easyCyte flow cytometer (among them, Annexin V-FITC : Ex=488nm, Em=525nm, PI: Ex=488nm, Em=620nm). The data were analyzed using FlowJo software, and the results were as follows: Figure 5 shown.

[0049] from Figure 5 It can be seen that after Annexin V-FITC / PI double staining, compared with the control group, early apoptosis occurred ...

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Abstract

The invention discloses use of nitazoxanide or pharmaceutically acceptable salt thereof in preparation of a drug for treating bladder cancers. The nitazoxanide or the pharmaceutically acceptable saltthereof is capable of inhibiting proliferation and clonality of different bladder tumor cell lines, so that the potential of a mitochondrial membrane is decreased, ROS is generated and increased, andapoptosis of bladder cancer cells is caused; meanwhile, the nitazoxanide or the pharmaceutically acceptable salt is capable of effectively inhibiting stemness maintenance of the bladder cancer cells;and the nitazoxanide and the pharmaceutically acceptable salt still have an effect of inhibiting growth of bladder tumors in vivo, appearances of reduction of activities and feeding and the like of nude mice do not appear under a therapeutic dose, and phenomenon of obvious sliming or death of the nude mice do not appear as well, so that the nitazoxanide and the pharmaceutically acceptable salt have better treatment and application prospects to the bladder cancers.

Description

technical field [0001] The invention relates to the new medical field of nitazoxanide, in particular to the use of nitazoxanide and a pharmaceutically acceptable salt thereof in the preparation of medicines for treating bladder cancer. Background technique [0002] Nitazoxanide (Nitazoxanide, NTZ) belongs to the derivatives of nitrothiasalicylic acid amide, its chemical name is 2-acetoxy-N-(5-nitro-2-thiazolyl)benzamide, which was originally approved by the US FDA For the treatment of various intestinal protozoan diseases. NTZ is a prodrug. Pharmacokinetic studies have shown that in blood, NTZ is deacetylated by plasma esterase and hydrolyzed into the active product tizoxanide (TIZ). The study found that the mechanism of action of NTZ may be that it inhibits the key metabolic enzyme in the process of anaerobic energy metabolism, that is, pyruvate: ferredox protease PFOR. PFOR can catalyze the oxidative dehydrogenation of pyruvate and produce acetyl-CoA and CO 2 . In term...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/426A61P35/00
CPCA61K31/426A61P35/00
Inventor 吴松孙海燕杨紫怡欧铜朱士茂
Owner SHENZHEN LUOHU PEOPLELS HOSPITAL
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