Application of celastrol in inhibiting tumor vasculogenic mimicry

A technology of tumor angiogenesis and tripterine, applied in antineoplastic drugs, organic active ingredients, medical preparations containing active ingredients, etc., can solve the problems that targeted therapy cannot effectively improve patient survival and the mechanism of action is unknown

Inactive Publication Date: 2020-04-10
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The existence of many angiogenesis pathways and VMs is the main reason why a single anti-tumor and anti-angiogenesis targeted therapy cannot effectively improve the survival of patients. It is urgent to find a method that can inhibit glioma angiogenesis through multiple pathways
Previous studies have found that tripterine can inhibit tumor growth and microvascular proliferation in glioma nude mice, but its specific mechanism is unknown and needs further study

Method used

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  • Application of celastrol in inhibiting tumor vasculogenic mimicry
  • Application of celastrol in inhibiting tumor vasculogenic mimicry
  • Application of celastrol in inhibiting tumor vasculogenic mimicry

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Embodiment 1 experimental material and method

[0029] 1. Experimental materials

[0030] 1) Drug preparation

[0031] Dissolve 8.05 mg of tripterycin in 402.5 μl of DMSO, filter and sterilize with a 0.22 μm microporous membrane to make a mother solution, and dilute with PBS to make a high dose of tripterycin (Celastrol high dose, Cel-H 2mg / kg ) group, medium dose (Celastrol medium dose, Cel-M 1mg / kg) group and low dose (Celastrol low dose, Cel-L 0.5mg / kg) group, the DMSO content was 1%. Temozolomide (TMZ) 35 mg was dissolved in 175 μl of DMSO, and then configured into 17.5 ml of TMZ solution (20 mg / kg).

[0032] LY294002: LY294002 is a highly selective inhibitor of PI3K in vivo. When used at a concentration of 50 μM, it can specifically attenuate PI3K activity, but does not inhibit other lipid and protein kinases. In this experiment, 1.5 mg LY294002 was added to 98 μl DMSO to prepare a 50 mM stock solution. Dilute to 50μM with complete medium when used.

[0033] ...

Embodiment 3

[0061] Example 3 Study on the Effect and Mechanism of Tripteryglide in Inhibiting VM Formation in U87 and U251 Glioma Cells

[0062] 3.1 CCK8 method was used to analyze the effect of tripterine on the viability of U87 and U251 cells. see results Figure 6 As shown in A, it can be seen that 0.5, 1 μM can inhibit the proliferation of U87 and U251 cells without affecting the activity of normal astrocytes.

[0063]3.2 Scratch test, Transwell chamber migration and invasion test to observe the effect of optimal dose of tripterine on the migration and invasion of U87 and U251 cells. see results Figure 6 As shown in B-D, tripterine 1 μM can significantly inhibit the migration and invasion of U87 and U251 cells.

[0064] 3.3 Observe the formation of VM in U87 and U251 cells and the influence of VE-cadherin expression under light microscope;

[0065] 1) Observe the formation of VM in U87 and U251 cells

[0066] Experimental preparation: Take out the Matrigel Matrigel stored at -20...

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Abstract

The invention illuminates the inhibition effect and mechanism of celastrol on glioma vasculogenic mimicry for the first time. Observation by PAS-CD31 double-staining method indicates that celastrol can inhibit the formation of nude mouse tumor tissue VM (vasculogenic mimicry) and also can lower the expression of naked mouse glioma mimicry related proteins EphA2 and VE-cadherin, and in-vitro experiments verify that celastrol can inhibit the formation of U87 and U251 glioma cell VM through a PI3K/AKT/mTOR pathway.

Description

technical field [0001] The invention relates to the field of tumor treatment, specifically inhibiting glioma by inhibiting the angiogenesis mimicry of glioma. Background technique [0002] In malignant glioma, there is a highly invasive tumor cell mimicking the lumen-like structure formed by endothelial cells——vasculogenic mimicry (VM). VM in vivo has the following characteristics: the vessel wall is mainly composed of tumor cells; there are no endothelial cells in the lumen, but a layer of basement membrane-like structure, central necrosis of the tumor is rarely seen around the VM, and red blood cells, platelets, etc. can be seen in the lumen It can be seen that VM has a blood supply function similar to that of endothelial blood vessels. Periodic acid-schiff stain (PAS)-platelet-endothelial cell adhesion molecule (platelet ECadhesion molecule-31, PECAM-1 / CD31) double staining showed that PAS was positive and CD31 was negative. [0003] The formation of VM is a complex bio...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/56A61K45/06A61K31/5377A61P35/00
CPCA61K31/5377A61K31/56A61K45/06A61P35/00A61K2300/00
Inventor 高伟王蕾朱迎君刘喜红
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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