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Use of homoharringtonine and harringtonine in inhibiting vascularization

An angiogenesis and drug technology, applied in the field of compounds, can solve the problems of limited anti-cancer effect, unclear anti-cancer mechanism, unreasonable dosage, etc., and achieve high curative effect, less drug resistance, and stable expression

Inactive Publication Date: 2008-06-25
PEKING UNIV FIRST HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although homoharringtonine and harringtonine have been used in the clinical treatment of tumors and have certain curative effects, their anticancer effects are limited due to their unclear mechanism of action and unreasonable doses.

Method used

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  • Use of homoharringtonine and harringtonine in inhibiting vascularization
  • Use of homoharringtonine and harringtonine in inhibiting vascularization
  • Use of homoharringtonine and harringtonine in inhibiting vascularization

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Example 1: Inhibitory effect of homoharringtonine and harringtonine on proliferation of human vascular endothelial cells.

[0024] Human umbilical vein endothelial cells (HUVEC, purchased from Cascade Biologics, Cot: C-003-5C) were cultured in Medium 200 (purchased from Cascade Biologics) containing 10% fetal bovine serum (FBS) (37°C, 5%CO 2 , 95% humidity), the fourth-generation cells were inoculated in a 96-well culture plate at a density of 4000 / 250ul, and a control group, a drug group with various concentration gradients and a blank control were set, and 3 replicate holes were made in each group. When the cell growth density reached 80%, 5 ul of homoharringtonine and harringtonine (dissolved in DMSO) were added respectively in various concentration gradients, so that the final concentrations were 100 uM, 10 uM, 5 uM and 1 uM respectively, and 5 ul of DMSO was added to the control group. After continuing to culture (M200 medium, 2% FBS) for 48 hours, add 5mg / ml tetr...

Embodiment 2

[0025] Example 2: Inhibitory effect of homoharringtonine and harringtonine on tube formation ability of human vascular endothelial cells.

[0026] Add BD Matrigel to each well of a 24-well culture plate TM Matrix original glue 200ul, make it polymerized into gel, the fourth generation human umbilical vein endothelial cell (HUVEC) suspension was inoculated into the 24-well plate coated with Matrigel glue at a density of 30000cell / 500ul, set the control group, each concentration gradient The medication group, the medication group were added with 10ul of homoharringtonine and harringtonine with a concentration gradient (wherein the concentrations of homoharringtonine were 0.25uM, 0.5uM, 1uM, 10uM respectively; Concentrations were 0.5uM, 1uM, 10uM, 100uM, dissolved in DMSO), the control group was added sterile DMSO 10ul, each group were made 3 replicate wells. 37°C, 5% CO 2 , 95% humidity for 24 hours, OLYMPUSCK40-RFL optical microscope to observe the formation of vascular endo...

Embodiment 3

[0027] Example 3: Inhibitory effect of homoharringtonine and harringtonine on migration ability of human vascular endothelial cells.

[0028] 1. Preparation of chemokines

[0029] The NIH3T3 cells that grew well the next day after passage were used. Gently rinse with serum-free DMEM twice. Serum-free DMEM, 5% CO 2 , 37°C for 24-48 hours. Collect the cell supernatant. Centrifuge (12000g, 4°C, 10min). Filter the supernatant (0.22um filter membrane) and store in aliquots (-20°C).

[0030] 2. Matrigel invasion test

[0031] Take 25ul of diluted Matrigel (the original glue was diluted with DMEM at a ratio of 1:2) and add it to the chamber on the Transwell plate to cover the entire surface of the polyester film, and incubate at 37°C for 30min to make Matrigel polymerize into a gel. The fourth-generation human umbilical vein endothelial cell (HUVEC) suspension was inoculated into the upper chamber at a density of 30000 / 250ul, washed 3 times with PBS, digested and harvested fro...

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Abstract

The present invention discloses the new use of homoharringtonine and harringtonine in inhibiting vasculariztion. Research probes the vasculariztion inhibiting effect of homoharringtonine and harringtonine. The technological scheme is that homoharringtonine and harringtonine are used in preparing medicine for prevention and / or treatment of inhibiting vasculariztion with the dosage being 0.03-0.1 mg / kg body weight / day and 0.05-0.1 mg / kg body weight / day separately. The present invention uses the vasculariztion as the target of treating diseases and has the advantages of treatment specificity of pointing newly formed vessel; small dosage, high treating effect and less side effect owing to the direct action of medicine to vascular endothelial cell; and less medicine resistance owing to relatively stable endothelial cell gene expression.

Description

technical field [0001] The present invention relates to a new application of the compound, in particular to a new application of homoharringtonine and harringtonine. Background technique [0002] Studies have shown that tumors themselves have the ability to initiate and promote angiogenesis to meet their own metabolism and nutrient supply needs. Tumor angiogenesis starts from the existing vascular bed. If there is no angiogenesis, the growth of the primary tumor will not exceed 1-2mm, and there will be no invasion and metastasis. Inhibiting tumor angiogenesis is closely related to blocking tumor occurrence, development, invasion and metastasis. Inhibiting tumor angiogenesis can also prevent the malignant transformation of precancerous lesions into cancer. Not only the growth, invasion and metastasis of solid tumors depend on angiogenesis, but also the growth and metastasis of hematological malignancies (such as malignant lymphoma, lymphocytic leukemia, etc.) are closely r...

Claims

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Application Information

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IPC IPC(8): A61K31/55A61P35/00A61P17/02A61P17/06A61P29/00A61P19/02A61P9/10
Inventor 王振军赵博
Owner PEKING UNIV FIRST HOSPITAL
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