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Application of triclabendazole in preparation of drugs for treating breast cancer

A technology for triclobendazole and breast cancer, which is applied in the field of preparation of drugs for treating breast cancer, can solve the problems of destroying cell permeability barrier, secondary necrotic cells, pyroptosis and the like

Inactive Publication Date: 2020-02-28
HANGZHOU HUIBO SCI & TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

GSDME-NT will then translocate and penetrate the plasma membrane, thereby disrupting the cell's permeability barrier, resulting in secondary necrosis / pyroptosis

Method used

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  • Application of triclabendazole in preparation of drugs for treating breast cancer
  • Application of triclabendazole in preparation of drugs for treating breast cancer
  • Application of triclabendazole in preparation of drugs for treating breast cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Example 1: Using breast cancer cells MCF-7 and MDA-MB-231 as cell models, verifying that triclabendazole induces apoptosis and lytic cell death in breast cancer cells:

[0025] To determine the effect of triclabendazole on breast cancer MCF-7 and MDA-MB-231 cells, breast cancer cells MCF-7 or MDA-MB-231 cells were treated with the indicated concentrations of triclabendazole (TRI) for 24 Hour. The CCK-8 assay was used to determine the cytotoxicity of the drug in these cells. Such as figure 1 Shown:

[0026] figure 1 In A and C are: MCF-7 and MDA-MB-231 cells were stained with Annexin V-FITC and PI, and then analyzed by flow cytometry. The proportion of cells shown in each quadrant of a representative dot plot of the flow cytometer.

[0027] figure 1 B and D in A and C are the quantitative analysis of the ratio of apoptotic cells to necrotic / suppurative cells, where the ordinate Annexin-V- / PI- represents living cells, Annexin-V+ / PI- represents apoptotic cells, Anne...

Embodiment 2

[0032] Example 2: Verification that triclabendazole induces breast cancer cell apoptosis through the intrinsic apoptosis pathway:

[0033]Triclobendazole is an effective apoptotic anti-fluke drug, which effectively exerts anti-fluke effect by destroying and interfering with the function of Tubulin. Cells were treated with 160 μM triclabendazole to try to further explore whether it can pass through the intrinsic apoptotic pathway Induces apoptosis in breast cancer cells.

[0034] First, mitochondria are labeled with a mito-tracker, which passively diffuses across the plasma membrane and accumulates in active mitochondria. The results showed that triclabendazole significantly decreased the activity of mitochondria in MCF-7 and MDA-MB-231 cells. In addition, mitochondrial membrane potential was detected using JC-1 staining, and the results showed that triclabendazole was able to reduce the level of JC-1 aggregates (red) and their ratio to JC-1 monomers (green), indicating a decr...

Embodiment 3

[0040] Example 3: Potential Mechanisms of Triclabendazole-Induced Apoptosis and Lytic Cell Death in Breast Cancer Cells:

[0041] MCF-7 cells were treated with trimendazole at the indicated concentrations for 24 hours, and protein markers of apoptosis were analyzed by Western blot, including Bax, bcl-2, cleaved-caspase-9, cleaved-caspase-8, cleaved-caspase-3 , cleaved-caspase-7 and cleaved-PARP.

[0042] Recently, gasdermin E (GSDME) has been shown to be a target protein of both intrinsic and extrinsic apoptotic pathways, and activated caspase-3 induces the formation of the GSDME-N domain (37 kDa) and targets the membrane to form holes, leading to pyroptosis. We next explored whether GSDME is expressed and cleaved to form the GSDME-N domain in drug-treated cells. Such as Figure 4 and Figure 5 Shown:

[0043] Figure 4 and Figure 5 A in A is a marker protein for detection of apoptosis and lytic cell death by Western blot; β-actin was used as a control.

[0044] Fig...

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Abstract

The invention relates to application of triclabendazole in preparation of drugs for treating breast cancer. According to the application of the triclabendazole in the preparation of the drugs for treating the breast cancer, the drugs for treating the breast cancer are tablets, granules, pills or capsules. Application of a triclabendazole composition in the preparation of the drugs for treating thebreast cancer is also included. Cancer cells of the to-be-treated breast cancer are MCF-7 or MDA-MB-231. The application has the advantages that the triclabendazole can induce apoptotic pyroptosis invitro and in vivo, and GSDME is cut by activated caspase-3 to generate GSDME-NT that take effects and forms vacuoles; the discovery suggests that the triclabendazole plays a role in cancer treatmentby inducing apoptosis of the cancer cells, specifically inducing GSDME-dependent apoptosis through the activated caspase-3 and at least partially through enhanced ROS / JNK / bax mitochondrial apoptosis pathways.

Description

technical field [0001] The invention relates to the field of preparation of drugs for treating breast cancer, in particular to the application of triclabendazole in the preparation of drugs for treating breast cancer. Background technique [0002] Breast cancer remains a major health problem and the leading cancer that threatens women's health. The most common cause of breast cancer is hereditary, but environmental and lifestyle factors can also increase the incidence of breast cancer, such as radiation, competitive and work stress, alcohol consumption, and obesity. Although great progress has been made in the treatment of breast cancer through the use of various therapies, including chemotherapy, endocrine therapy, and radiotherapy; however, the overall response rate of chemotherapy in breast cancer patients is not ideal, and adverse reactions occur concurrently. Indeed, these therapies eventually become refractory mainly due to the development of resistance to apoptosis. ...

Claims

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Application Information

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IPC IPC(8): A61K31/4184A61P35/00
CPCA61K31/4184A61P35/00
Inventor 柳毅颜亮吴刚
Owner HANGZHOU HUIBO SCI & TECH CO LTD
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