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Application of GBE1 inhibitor flavopiridol and pharmaceutical composition thereof in preparing medicine for treating lung adenocarcinoma

A technique for flapingometry and lung adenocarcinoma, applied in the field of medicine, can solve problems such as no reports on the therapeutic effect of lung adenocarcinoma, and achieve the effect of enhancing chemotherapy sensitivity and obvious time-dependent effect.

Active Publication Date: 2020-03-13
THE FIRST AFFILIATED HOSPITAL OF ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] However, there has been no report on the inhibitory effect of flavandol on GBE1, and no report on the therapeutic effect of flavandol or its pharmaceutical composition on lung adenocarcinoma.

Method used

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  • Application of GBE1 inhibitor flavopiridol and pharmaceutical composition thereof in preparing medicine for treating lung adenocarcinoma
  • Application of GBE1 inhibitor flavopiridol and pharmaceutical composition thereof in preparing medicine for treating lung adenocarcinoma
  • Application of GBE1 inhibitor flavopiridol and pharmaceutical composition thereof in preparing medicine for treating lung adenocarcinoma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Example 1: Research on the Inhibitory Effect and Mechanism of Flavapine on the Proliferation of Lung Adenocarcinoma Cells

[0025] 1. Experimental method

[0026] 1. Cell culture

[0027] Human lung adenocarcinoma A549 cells (frozen in our laboratory) were cultured in RPMI 1640 medium (HyClone; Thermo Fisher Scientific) in 5% CO 2 , cultured and passaged in a 37°C incubator, and the logarithmic phase cells were taken for subsequent experiments.

[0028] 2. Determination of cell proliferation activity by CCK-8 method

[0029] Follow the instructions of the CCK-8 kit (Dojindo, Japan). Digest the A549 cells in the logarithmic growth phase with trypsin, make a cell suspension, inoculate 2000 cells per well in a 96-well plate, add 100 μl medium to each well, and place at 37°C, 5% CO 2 Adhere overnight in the incubator. Set drug concentrations of 10, 20, 50, 100, 200, 400, 500, 1000, 2000nM respectively Flappin group, negative control group (drug concentration is 0μM) a...

Embodiment 2

[0050] Example 2: The sensitization effect of schisandra ketone alcohol on the inhibition of lung adenocarcinoma cell proliferation by flapine

[0051] 1. Experimental method

[0052] "CCK-8 method for measuring cell proliferation activity" is the same as in Example 1, specifically as follows:

[0053] Follow the instructions of the CCK-8 kit (Dojindo, Japan). Digest the A549 cells in the logarithmic growth phase with trypsin, make a cell suspension, inoculate 2000 cells per well in a 96-well plate, add 100 μl medium to each well, and place at 37°C, 5% CO 2 Adhere overnight in the incubator. Set up a series of drug concentrations of flapine, a series of drug concentrations of schisandra ketone alcohol, a series of concentrations of flapine ketone + 20nM schisandra ketone 1 group, a series of concentrations of flapine ketone + 50nM schisandra ketone composition 2 groups , negative control group (drug concentration is 0 μ M) and blank control group, each group is set 3 duplic...

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Abstract

The invention discloses application of a GBE1 inhibitor flavopiridol and its pharmaceutical composition in preparing a medicine for treating lung adenocarcinoma. According to the invention, it is found that flavopiridol can effectively inhibit the proliferation of lung adenocarcinoma cells, and the dose-dependent and time-dependent effects are obvious. According to the results of WB and Moleculardocking, flavopiridol may play a role in inhibiting the proliferation of lung adenocarcinoma cells by inhibiting GBE1, and flavopiridol may be an effective GBE1 inhibitor. Schisandrone alcohol, a compound that may participate in the regulation of GBE1 pathway, cannot directly inhibit the proliferation of lung adenocarcinoma cells, but can enhance the sensitivity of lung adenocarcinoma cells to chemotherapy of flavopiridol. Therefore, flavopiridol and Schisandrone alcohol can be used as a pharmaceutical composition to prepare an anti lung adenocarcinoma pharmaceutical preparation for the treatment of lung adenocarcinoma.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to the application of a GBE1 inhibitor frapidox and its pharmaceutical composition in the preparation of medicines for treating lung adenocarcinoma. Background technique [0002] Glycogen branching enzyme (glucogen branching enzyme 1, GBE1) protein molecule is a member of the α-amylase family, mainly involved in the formation of glycogen branching in human cells, and is one of the main enzymes in the process of glycogen formation. It is generally believed that the formation of glycogen branches, on the one hand, increases the water solubility of glycogen, which is beneficial to its storage; on the other hand, it can provide docking sites for glycogen-binding proteins, including glycogen metabolism-related enzymes and regulatory proteins. Glycogen is the main energy storage substance of cells, and the level of glycogen is significantly increased in various tumors such as colon can...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/122A61P35/00A61K31/513
CPCA61K31/122A61K31/513A61P35/00A61K2300/00
Inventor 李砺锋赵杰张毅袁永亮薛文华
Owner THE FIRST AFFILIATED HOSPITAL OF ZHENGZHOU UNIV
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