New drug use of pristimerin

A technology of platyphyllin and its use, applied in the field of medicine, can solve the problems such as the application report of PRISEphB4/Ephrin-B2 signaling pathway inhibitor, etc., and achieve the effect of inhibiting tumor proliferation

Inactive Publication Date: 2020-07-10
THE FIRST AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, it has been reported that PRIS can be used as a proteasome inhibitor, but ther...

Method used

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  • New drug use of pristimerin
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  • New drug use of pristimerin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1, PRIS inhibits the EphB4 / Ephrin-B2 signaling pathway

[0039] (1) CRLC cells were treated with various concentrations of PRIS (0, 2, 4, 8 μM) for 24 hours, and detected by Western blot, the results were as follows figure 1 As shown, PRIS inhibited the expression of EphB4 / Ephrin-B2 signaling pathway molecules EphB4 and Ephrin-B2 in a dose-dependent manner; the results of immunofluorescence staining were as follows: figure 2 As shown, EphB4 is expressed in the nucleus, and PRIS inhibits the expression level of EphB4 in the nucleus.

[0040] (2) NVP-BHG712 is a specific kinase inhibitor of EphB4, which can inhibit the autophosphorylation of EphB4, thereby inhibiting the forward transmission of EphB4 / Ephrin-B2 signal. CRLC cells were treated with PRIS and / or NVP-BHG712, and the results of Western blot detection were as follows image 3 As shown, NVP-BHG712 (0.1μM) significantly inhibited the expression of EphB4 and Ephrin-B2, and the EphB4 / Ephrin-B2 signaling p...

Embodiment 2

[0043] Example 2, PRIS acts as an inhibitor of EphB4 / Ephrin-B2 signaling pathway to inhibit cell proliferation, cell migration, and formation of vascular structures

[0044] (1) Analyze CRLC cells and normal human bronchial epithelial cells BEAS-2B, the results of mRNA analysis and western blot are as follows Image 6 As shown, compared with normal human bronchial epithelial cells, EphB4 is highly expressed in CRLC, which indicates that there is abnormal activation of EphB4 / Ephrin-B2 signaling pathway in non-small cell lung cancer.

[0045] (2) Use PRIS and / or NVP-BHG712 to treat CRLC cells, and the cell proliferation test results are as follows Figure 7 As shown, both PRIS and NVP-BHG712 (0.1 μM) inhibited the proliferation of CRLC cells through EphB4 / Ephrin-B2 signaling pathway inhibition.

[0046] (3) CRLC cells were transfected with PRIS and / or EphB4 siRNA, and the detection results of cell proliferation, cell migration, and in vitro lumen formation ability were as follo...

Embodiment 3

[0048] Example 3. PRIS promotes cell apoptosis by inhibiting EphB4 / Ephrin-B2 signaling pathway.

[0049] (1) Use PRIS as the EphB4 / Ephrin-B2 signaling pathway inhibitor to treat CRLC cells, and the results of cell apoptosis are as follows Figure 9 As shown, PRIS significantly promoted the apoptosis of CRLC cells ( Figure 9 A), measured by caspase activity, PRIS significantly increased the activity of caspase-9, caspase-3 and caspase-4 in a dose-dependent manner ( Figure 9 B), measured by caspase expression level, PRIS significantly increased the expression levels of activated caspase-9, activated caspase-3 and activated caspase-4 and cytochrome c ( Figure 9 C), caspase inhibitors include Z-LEHD-FMK for caspase-9 inhibition, Z-DEVD-FMK for caspase 3 inhibition, and Ac-LEVD-CHO for caspase 4 inhibition, such as Figure 9 As shown in D, these inhibitors all reversed the apoptosis promoted by PRIS, and it can be seen that PRIS promotes apoptosis by activating caspase.

[00...

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Abstract

The invention discloses a new use of pristimerin in preparation of an EphB4/Ephrin-B2 signal pathway inhibitor. The EphB4/Ephrin-B2 signal pathway inhibitor can treat diseases caused by EphB4/Ephrin-B2 signal pathway abnormal activation, particularly tumor proliferation and migration a non-small cell lung cancer, angiogenesis, and anti-apoptotic effects caused by EphB4/Ephrin-B2 signal pathway abnormal activation.

Description

technical field [0001] The present invention belongs to the field of medicine, and more specifically relates to the use of phylagenin and / or its derivatives as signal pathway inhibitors. Background technique [0002] EphB4 / Ephrin-B2 signaling pathway molecules include EphB4 (Ephrin type-B receptor4) as a receptor and Ephrin-B2 as a ligand; EphB4 and Ephrin-B2 can be mutually activated, that is, the interaction between the receptor and the ligand Signal transduction is bidirectional. Generally, Ephrin-B2 activates EphB4 as a forward signal, and EphB4 activates Ephrin-B2 as a reverse signal. EphB4 / Ephrin-B2 signaling pathway is closely related to nervous system development, physiological and pathological angiogenesis, and tumor development. [0003] Pristimerin (PRIS for short, CAS No. 1258-84-0) is a natural quinonemethyl triterpenoid isolated from various plants of Chenopodiaceae and Hippophaeaceae. Inflammatory, antiperoxidative, antioxidant, antimalarial, antifungal and ...

Claims

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Application Information

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IPC IPC(8): A61K31/56A61P35/00A61P35/04
CPCA61K31/56A61P35/00A61P35/04
Inventor 陈孝唐欲博黄帅陈杰邹学农
Owner THE FIRST AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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