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Screening for CXCR4 receptor antagonism polypeptides for treating breast carcinoma and its uses

A breast cancer, antagonistic technology, applied in the field of anti-breast cancer metastasis drugs, can solve the problems of screening and application methods of CXCR4 receptor antagonistic polypeptides that have not been seen in breast cancer, achieve inhibition of axillary lymph nodes and lung metastasis, and reduce side effects , Improve the effect of radiotherapy concentration

Inactive Publication Date: 2008-12-31
BENGBU MEDICAL COLLEGE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] After extensively consulting various public publications and medical textbooks at home and abroad, and extensively searching the patent data of various countries in the world, there is no invention of the screening and application method of the CXCR4 receptor antagonistic polypeptide for the treatment of breast cancer identical to the present invention, especially Sentinel lymph node detection after radiolabeling and postoperative targeted radiotherapy

Method used

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  • Screening for CXCR4 receptor antagonism polypeptides for treating breast carcinoma and its uses
  • Screening for CXCR4 receptor antagonism polypeptides for treating breast carcinoma and its uses
  • Screening for CXCR4 receptor antagonism polypeptides for treating breast carcinoma and its uses

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Example 1, multiple sequence comparison analysis of vMIP-II and CXCR4 receptor binding factor:

[0052] First select the human-derived chemokine sequence that specifically binds to the CXCR4 receptor for structure-based multiple sequence alignment analysis, and the residues that exist in all chemokine sequences may be the residues related to the receptor binding ( That is, the establishment of the standard binding residue model). Then the sequence of vMIP-II was introduced into the standard binding residue model for multiple sequence comparison analysis to obtain the residues related to the binding of vMIP-II to the receptor, that is, the residues highly related to the binding of vMIP-II to the receptor. We compared the protein sequences of several chemokines obtained from NCBI (including IL-8, SDF-1α, MIP-1β, RANTES). From the results, it can be seen that the C-terminus of chemokines has three antiparallel α-helices surrounded by β-sheets, with a large amount of charg...

Embodiment 2

[0054] Example 2, preparation of NT21MP.

[0055] The polypeptide described in the present invention obtains the binding site between vMIP-II and CXCR4 receptor on the basis of bioinformatics analysis, and then obtains it through a chemical synthesis method.

Embodiment 3

[0056] Example 3, NT21MP down-regulates the CXCR4 receptor expressed on the surface of breast cancer cells.

[0057] After SK-BR3 and MCF-7 breast cancer cell lines were treated with different concentrations of NT21MP, immunohistochemistry, RT-PCR and Western blot were used to detect the effect of NT21MP on the expression of CXCR4 receptor protein on the cell surface. The experimental results showed that, compared with the negative control group, NT21MP could significantly reduce the expression of CXCR4 in cells.

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Abstract

The invention provides a screening and modification method, a marker and an application of polypeptide drugs which are used in the treatment of CXCR4 receptor-mediated breast cancer. A human chemokine SDF-1 Alpha and the homology region of a human herpes virus 8 MIP-II are compared, thereby obtaining a binding site of vMIP-II and CXCR4 receptor and further obtaining a CXCR4 specific binding active peptide. With the role of specific binding CXCR4 and the blocking of the physiological binding of the SDF-1 Alpha and the CXCR4, the CXCR4 specific binding active peptide is a high-efficient and specific chemokine receptor antagonist. The chemotactic activity of wide type SDF-1 Alpha to breast cancer cells and the growth of the breast cancer cells can be inhibited, and the growth and the metastasis of the CXCR4-positive tumor cells are simultaneously inhibited, thereby having the dual-target effect. The invention further provides a marked polypeptide to be targetedly positioned in sentinel lymph node and metastatic site, thereby being used in the detection and the targeted radiotherapy of the metastatic status of the sentinel lymph node before and in the operation of the breast cancer.

Description

technical field [0001] The invention relates to an anti-breast cancer metastasis drug, in particular to the screening and application of a CXCR4 receptor antagonistic polypeptide for treating breast cancer. Background technique [0002] The incidence of breast cancer has gradually risen to the first place among female malignant tumors. Breast cancer cells become deadly only when they metastasize to vital organs such as the liver and lungs. The best way to reduce mortality is early detection and early treatment. Inventing a method for early detection and treatment of breast cancer is very important for saving the lives of breast cancer patients and is an important task of modern medical science. [0003] Modern medical research believes that the establishment and growth of metastases at distant sites depend on the interaction between tumor cells and the host environment. Metastasis is the result of several sequential steps and is an organ-selective process. In 2001, Mulle...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/68A61K38/00
Inventor 杨清玲丁勇兴陈昌杰
Owner BENGBU MEDICAL COLLEGE
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