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Vascular endothelial growth factor C antagonistic polypeptide and application thereof

A technology of growth factor and vascular endothelium, which is applied in the field of polypeptides for the treatment of acute lymphoblastic leukemia, to achieve the effect of improving the survival rate

Inactive Publication Date: 2015-06-10
SUZHOU PULUODA BIOLOGICAL SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Currently, there is no well-developed vascular endothelial growth factor-C antagonistic polypeptide available for the treatment of acute lymphoblastic leukemia

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] Effect of vascular endothelial growth factor C antagonistic polypeptide on the affinity between vascular endothelial growth factor C receptor and vascular endothelial growth factor C in vitro.

[0016] Human lymphatic endothelial cells growing logarithmically at 1.0×10 5 Add it into a 96-well culture plate and incubate for 24 hours. Add different concentrations of the experimental drug vascular endothelial growth factor C antagonistic polypeptide (Shanghai Sangong Synthetic) and the positive control drug vincristine to the experimental wells and positive drug control wells; add the same volume to the blank group solvent, while adding 125 I-labeled vascular endothelial growth factor C. Five replicate wells were set up in each well, and cultured for 48 hours. Wash away the supernatant, calculate the radiation intensity with a ?-liquid scintillation counter, and judge the binding force between the vascular endothelial growth factor C receptor and the vascular endothelial...

Embodiment 2

[0018] IC50 of vascular endothelial growth factor C antagonistic polypeptide on the growth and survival of human lymphatic endothelial cells cultured in vitro.

[0019] Using the MTT colorimetric method. Human lymphatic endothelial cells growing logarithmically at 1.0×10 5 Add it to a 96-well culture plate and incubate for 24 hours. Add different concentrations of the experimental drug vascular endothelial growth factor C antagonistic polypeptide and the positive control drug paclitaxel to the experimental wells and positive drug control wells; add the same volume of solvent to the blank group. Set up five duplicate wells per well, culture for 48h, add MTT to each well at 0h, 2h, 8h, 14h, 20h, 24h, 36h, and 48h respectively, add DMSO after 4h, incubate for 30min, and incubate at 620nm in a microplate reader. Measure the absorbance A value, according to the formula human lymphatic endothelial cell growth inhibition rate=(1-absorbance value of experimental group / absorbance valu...

Embodiment 3

[0021] The in vivo activity of vascular endothelial growth factor C antagonistic polypeptide was detected by tumor model.

[0022] The U937 tumor model was established, and the positive control drug paclitaxel was added; the same volume of solvent was added to the blank group, and 3 doses were set to the experimental group: 0.75, 1.5, and 3 mg / Kg. After 21 days, the number of surviving mice was observed, and the survival rate was calculated. The results showed that the antagonistic polypeptide of vascular endothelial growth factor C can effectively protect mice and improve the survival rate of tumor-bearing mice, with the survival rate reaching 86.9%.

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Abstract

The invention relates to the field of medicines, in particular to polypeptide for restraining vascular endothelial growth factors C and treating acute lymphocytic leukemia. The sequence of the polypeptide is GPREGPKPLSQCVCKHHQ which is brand new, the polypeptide can restrain the vascular endothelial growth factors C in vitro on the 1 micromole level, the survival rate of tumor-bearing mice in in-vivo tests is improved, and the polypeptide has potential new drug development value.

Description

technical field [0001] The invention relates to vascular endothelial growth factor C antagonistic polypeptide and application thereof, in particular to a polypeptide capable of inhibiting vascular endothelial growth factor C for treating acute lymphocytic leukemia. Background technique [0002] Acute lymphoblastic leukemia (ALL) is a progressive malignant disease characterized by large numbers of immature white blood cells that resemble lymphoblasts. These cells can be found in the blood, bone marrow, lymph nodes, spleen and other organs. Acute lymphoblastic leukemia accounts for 80% of acute leukemia in children, and the peak incidence is between 3 and 7 years old. The greatest threat to patients with ALL is spread and metastasis. How to eliminate distant metastasis of a certain cancer or prevent recurrence is an indispensable part of cancer treatment, and it is also a hot issue in the treatment of acute lymphoblastic leukemia currently being discussed. [0003] Lymph is...

Claims

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Application Information

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IPC IPC(8): C07K7/08A61K38/10A61P35/02
Inventor 罗瑞雪
Owner SUZHOU PULUODA BIOLOGICAL SCI & TECH
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