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Application of polysaccharide EGFR inhibitor for targeted inhibition of tumor metastasis and preparation method of polysaccharide EGFR inhibitor

A technology of tumor metastasis and polysaccharides, which is applied in the field of medicine, can solve the problems of poor inhibitory effect of wild-type EGFR, drugs for patients with EGFR mutations, blocking EGFR dimerization, etc., to prevent tumor cell invasion, low toxicity, and easy access Effect

Pending Publication Date: 2020-08-18
MINJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, with the continuous research and development of EGFR inhibitors, there have been many problems such as narrow drug application range, poor inhibitory effect on wild-type EGFR, continuous mutation of EGFR in patients, and drug toxicity.
In addition, current EGFR inhibitors mainly inhibit cell proliferation by blocking the activation of intracellular tyrosine kinases, but cannot directly block the dimerization of EGFR from outside the cell, thus inhibiting the activation of EGFR

Method used

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  • Application of polysaccharide EGFR inhibitor for targeted inhibition of tumor metastasis and preparation method of polysaccharide EGFR inhibitor
  • Application of polysaccharide EGFR inhibitor for targeted inhibition of tumor metastasis and preparation method of polysaccharide EGFR inhibitor
  • Application of polysaccharide EGFR inhibitor for targeted inhibition of tumor metastasis and preparation method of polysaccharide EGFR inhibitor

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Effect test

Embodiment 1

[0030] Example 1. Extraction and analysis of polysaccharides

[0031] The Achyranthes bidentata polysaccharide used in the present invention is extracted by the inventor in his unit. Achyranthes bidentata powder (Achyranthes bidentata produced in Henan) was taken, dissolved in deionized water, mixed evenly, filtered and extracted for 3 hours, and crude polysaccharide was obtained by fractional precipitation with ethanol. Add sevage reagent to the crude polysaccharide to remove protein, and obtain a single pure Achyranthes bidentata polysaccharide through CM-Sephadex C50 and Sephadex G50 fiber column chromatography. Fehling's reagent reaction result is a red precipitate to prove that it contains sugars and glycosides and other components, while Libermann-Burchard reaction, Sarkovsky reaction, Hager reaction and potassium bismuth iodide reaction have no obvious color change, the above The results proved that the extracted Achyranthes bidentata polysaccharides were pure polysacc...

Embodiment 2

[0035] Example 2. Detection of the EGFR activation inhibitory effect on the EGFR wild-type cell line A549 and the EGFR mutation-sensitive cell line PC-9

[0036] The inventor detected the phosphorylation level of EGFR, ie the activation of EGFR kinase, by Western blot experiment. Cells A549 and PC-9 in the logarithmic growth phase were inoculated in 6-well plates, and when the cells grew to about 80%, they were pretreated with different concentrations of polysaccharides (0, 10, 50, 100 μg / mL) for 24 hours, and transferred to 6-well plates. After being stimulated by adding EGF (50ng / mL) for 15min, the cells were collected. Add protein lysate RIPA, protease inhibitor PMSF and phosphatase inhibitor, lyse on ice for 30 min, and centrifuge to collect protein lysate. The EGFR kinase activity (ie, the expression level of p-EGFR) was detected by SDS-polyacrylamide gel electrophoresis, membrane transfer, antibody incubation, color development and other steps, and the results shown in ...

Embodiment 3

[0041] Example 3 Molecular docking predicts the binding site between polysaccharide and EGFR

[0042] The binding site of polysaccharide and EGFR was analyzed by computer model, and the structure of EGFR (1IVO) was derived from the protein database. Docking by computer simulation showed that the binding site of polysaccharide and EGFR was between domains I and III of EGFR.

[0043] Molecular docking analysis to find the binding sites of polysaccharides and EGFR, such as figure 2 As shown, the binding site of polysaccharides to EGFR is located between domains I and III, which blocks the binding of EGFR to EGF, and the lowest affinity is -9.08275. Polysaccharides occupy the binding site of EGF in the form of ligands, thereby blocking the combination of EGF and EGFR, inhibiting the dimerization of EGFR and the activation of intracellular kinases, which also explains why EGF loses its function in the presence of polysaccharides. Activation of EGFR.

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Abstract

The invention provides an application and preparation method of a polysaccharide EGFR inhibitor for targeted inhibition of tumor metastasis. The EGFR inhibitor provided by the invention is extracted from the traditional Chinese medicine achyranthes aspera, has the characteristics of high efficiency and low toxicity, and can be used for preventing cancer cell metastasis. The EGFR inhibitor providedby the invention can effectively inhibit the transfer of EGFR wild type cells A549 and mutation sensitive type cells PC-9. Therefore, the EGFR inhibitor can be used for treating EGFR wild type and mutation sensitive type lung cancer patients, and has small toxic and side effects.

Description

technical field [0001] The invention belongs to the field of medicines, and in particular relates to the application and preparation method of a polysaccharide EGFR inhibitor targeting tumor metastasis inhibition. Background technique [0002] Cancer is the second leading cause of human death after cardiovascular disease. According to statistics, in 2020, there will be about 1.8 million new cancer cases in the United States, while the number of deaths will be as high as 600,000, of which 21% will be died of lung cancer. About 57% of the patients diagnosed with lung cancer have metastasized, resulting in less than 5% of the patients' 5-year survival period, which is also the main factor for the high mortality rate of cancer. In recent years, a variety of targeted drugs for the terminal stage of cancer have been developed. Although the early clinical effects are remarkable, with the mutation of genes and the increasing drug resistance, the development of targeted drugs has re...

Claims

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Application Information

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IPC IPC(8): A61K31/715A61P35/04C08B37/00
CPCA61K31/715A61P35/04C08B37/0003C08B37/006
Inventor 钟春莲卢余盛贾力
Owner MINJIANG UNIV
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