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Application of niclosamide or pharmaceutically acceptable salt thereof in pharmacy

A niclosamide and pharmaceutical technology, which is applied in the field of preparing radiosensitizing preparations for treating malignant tumors, can solve problems such as enhancing tumor cells, and achieve the effects of reducing recurrence rate, improving effect and enhancing radiosensitivity

Inactive Publication Date: 2015-10-14
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

There are no relevant reports at home and abroad about the use of niclosamide or its pharmaceutically acceptable salts in enhancing the sensitivity of tumor cells to radiation.

Method used

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  • Application of niclosamide or pharmaceutically acceptable salt thereof in pharmacy
  • Application of niclosamide or pharmaceutically acceptable salt thereof in pharmacy
  • Application of niclosamide or pharmaceutically acceptable salt thereof in pharmacy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Inhibitory effect of niclosamide on the proliferation of human triple-negative breast cancer cells MDA-MB-231, Hs578T and non-triple-negative breast cancer cells T47D, MCF-7:

[0034] MTT assay was used to detect the inhibitory effect of niclosamide on the growth of the four human breast cancer cell lines: the logarithmic growth phase cells were taken in 4×10 cells per well. 4 Cells / 100 μl were inoculated in 96-well plates. After the cells adhered to the wall, different concentrations of niclosamide were added, and a culture medium blank control group was set up. 200 μl of culture solution, discard the supernatant after continuing to cultivate for 4 hours, add 150 μl of dimethyl sulfoxide (DMSO), shake for 15 minutes, and measure the absorbance (A) value of each well at 490 nm with a Swiss TECAN infiniteM200 multifunctional microplate reader, as follows The formula calculates the inhibition rate of niclosamide to cells: cell inhibition rate (%)=1―[(A 实验 -A 空白 ) / (A 对照...

Embodiment 2

[0036] Effects of niclosamide on radiosensitivity of MDA-MB-231, Hs578T, T47D, MCF-7 cells:

[0037] The influence of niclosamide on the radiosensitivity of cells was detected by colony formation assay, and the IC of various cells were detected by niclosamide respectively. 50 The concentration below 20% of the radiosensitivity drug concentration was taken as the concentration of the radiosensitive drug: the cells in the logarithmic growth phase were digested with 0.25% trypsin to make a single cell suspension, diluted to different cell concentration gradients, and seeded in 60mm culture dishes. Different concentrations of niclosamide were added and cultured for 24 hours, and a DMSO solvent control group was set at the same time, and then 0, 2, 4 and 6 Gy of irradiation were given, and the culture was continued for 10 to 14 days. The number of clones larger than 50 cells was counted under a microscope. Carry out the following calculations: adherence rate (%) = (number of clones...

Embodiment 3

[0040] Effects of niclosamide combined with irradiation on the expression of p-β-catenin (S675), β-catenin and the downstream target protein Cyclin D1 in MDA-MB-231 cells:

[0041] MDA-MB-231 cells in the logarithmic growth phase were inoculated into 60mm culture dishes, and divided into DMSO solvent control group, simple niclosamide administration group (1.0, 1.5, 2.0 μmol / L), simple irradiation group (6Gy) Combined with niclosamide irradiation group (1.0μmol / L+6Gy, 1.5μmol / L+6Gy, 2.0μmol / L+6Gy), 6h after irradiation, cells were collected, protein was extracted after lysis, and protein content was detected by WesternBlot The protein expressions of p-β-catenin (S675), β-catenin and Cyclin D1 were detected by the method, and the Western blot bands were collected and analyzed by the Chemi Doc XRS digital imaging system of Bio-Rad, USA. The results showed that adding 1.0, After the cells were pretreated with 1.5 and 2.0 μmol / L niclosamide for 24 hours, the expressions of p-β-cate...

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Abstract

The invention belongs to the technical field of medicines, relates to a new medical application of niclosamide or a pharmaceutically acceptable salt thereof, and in particular relates to niclosamide or a pharmaceutically acceptable salt thereof in preparation of a malignant tumor radiosensitization preparation. A test shows that niclosamide has an effect of enhancing the radiosensitivity of triple-negative breast cancer cells when the concentration of niclosamide is less than 20%IC50 and is nontoxic to the triple-negative breast cancer cells, the mechanism of niclosamide is related with a Wnt / beta-catenin signal channel for inhibiting ionizing radiation induction, the activation of AKT and the repair of DNA double strand break, a safe and effective radiosensitization new medicament especially a radiosensitization preparation for treating malignant tumor can be further prepared, and the preparation has important significance for improving the radiotherapy effect of triple-negative breast cancer, reducing the relapse rate and improving the survival rate.

Description

technical field [0001] The invention belongs to the technical field of medicine. The invention relates to a new medical use of niclosamide or a pharmaceutically acceptable salt thereof, specifically relates to the use of niclosamide or a pharmaceutically acceptable salt thereof in preparing radiosensitizing preparations for treating malignant tumors. Background technique [0002] According to reports, breast cancer is the malignant tumor with the highest incidence rate in women, and its incidence rate is on the rise worldwide and tends to be younger. Radiation therapy, as an important treatment method, has been generally affirmed in reducing the local recurrence rate after breast cancer surgery and improving the survival rate of patients. However, high genetic heterogeneity makes some breast cancers, especially triple-negative breast cancer (TNBC), less effective. TNBC refers to breast cancer with negative expression of estrogen receptor (ER), progesterone receptor (PR) an...

Claims

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Application Information

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IPC IPC(8): A61K31/167A61P35/00A61P15/14
Inventor 陈红红殷丽娜张旭霞王晶暴一众高赟胡昱兴徐爱红
Owner FUDAN UNIV
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