CN104693284A - Platelet-derived-growth-factor antagonistic polypeptide and application thereof - Google Patents
Platelet-derived-growth-factor antagonistic polypeptide and application thereof Download PDFInfo
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- CN104693284A CN104693284A CN201510157258.7A CN201510157258A CN104693284A CN 104693284 A CN104693284 A CN 104693284A CN 201510157258 A CN201510157258 A CN 201510157258A CN 104693284 A CN104693284 A CN 104693284A
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- growth factor
- derived growth
- platelet derived
- polypeptide
- platelet
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Abstract
The invention relates to the field of drugs, in particular to polypeptide which is used for suppressing platelet-derived growth factor receptors and can treat liver cancers. The sequence of the polypeptide is MKVSIMDKGRFSVKTVHRQAP and is a brand new sequence. The polypeptide has the advantages that the liver cancers can be prevented and treated, and the potential new drug development value is achieved.
Description
technical field:
The present invention relates to pharmaceutical field, be specifically related to the platelet derived growth factor antagonism polypeptide for prevention and therapy liver cancer.
background technology:
Liver cancer and liver malignancy are the common disease in surgical disease and frequently-occurring disease.Because liver is the maximum parenchymatous organ of human body, bear all kinds of important metabolic function of human body, therefore, liver is once occur that malignant tumour will cause not and the serious consequence of life.Again because liver has abundant supply of blood flow, as in close relations in postcava, portal vein, biliary system etc. with the important feature of human body; Liver malignancy incidence of occult, invasive growth is quick, its treatment very difficulty.Therefore, early discovery, early diagnosis, early treatment is needed.Think that its morbidity is complex process that is multifactor, multi-step at present, by environment and therefore double factor affect.Research is thought, the hepatic fibrosis that liver injury causes, and causes liver cirrhosis, finally develops into liver cancer.In this course, platelet derived growth factor (PDGF) plays an important role.
PDGF is a kind of important factor,mitogenic, has the ability stimulating specific cells group division growth.When liver is impaired, the PDGF of a large amount of secretion stimulates interstitial stellate cell propagation, is converted into myofiber sample parent cell, and impels stellate cell to move, be gathered in inflammation damaged zone.And myofiber sample parent cell synthesizes a large amount of extrtacellular matrix deposition in liver cell matrix, promote that hepatic fibrosis occurs.PDGF can promote that myofibroblast produces collagen, and especially I type and III Collagen Type VI, cause liver cirrhosis.PDGF also suppresses the effect of collagenase by raising tissue inhibitor of metalloproteinase (TIMP-1), to reduce the degraded of extracellular matrix.Therefore, suppress PDGF, the formation that can reduce collagen can be reduced, promote that collagenase is to the degraded of collagen, thus the hepatic fibrosis suppressing liver injury to cause and liver cirrhosis, the final generation reducing liver cancer.
At present, the inhibitor of target PDGF has become the study hotspot developing emerging anti-liver cancer.However, the platelet derived growth factor antagonism polypeptide of unripe exploitation comes out, for prevention and therapy liver cancer.
summary of the invention:
The present invention seeks to, for a kind of platelet derived growth factor antagonism polypeptide of design, to may be used for prevention and therapy liver cancer.
Technical solution of the present invention is to provide a kind of platelet derived growth factor antagonism polypeptide, and its sequence is MKVSIMDKGRFSVKTVHRQAP, and the application in prevention and therapy liver-cancer medicine.
Principle of the present invention is platelet derived growth factor antagonism polypeptide and platelet derived growth factor receptors bind, platelet derived growth factor acceptor is suppressed to produce the effect of physiology or pathology, T suppression cell intracellular domain tyrosine residues autophosphorylation, thus signal is imported in cell, the vital movement of regulating cell, comprise the division growth of liver cancer cell, thus play the effect of Hepatoma therapy.
beneficial outcomes:
Platelet derived growth factor Antagonist PolYpeptide Sequences MKVSIMDKGRFSVKTVHRQAP in the present invention, can targeted inhibition platelet derived growth factor acceptor, and the physiology suppressing platelet derived growth factor to produce or the effect of pathology, reach the effect of prevention and therapy liver cancer.
Embodiment
Embodiment 1
Platelet derived growth factor antagonism polypeptide is on the impact of external platelet derived growth factor acceptor and platelet derived growth factor avidity.
By the HepG2 cell of logarithmic growth, with 1.0 × 10
5add in 96 well culture plates, cultivate 24h, experimental port, positive drug control hole add Experimental agents platelet derived growth factor antagonism polypeptide (the raw work synthesis in Shanghai) and the positive control medicine vincristine(VCR) of different concns respectively; Blank group adds the solvent of same volume, adds meanwhile
125the platelet derived growth factor of I mark.Five multiple holes are established in every hole, cultivate 48h.Wash away supernatant liquor, use-liquid scintillation counter calculates intensity of radioactivity, and judge the bonding force of platelet derived growth factor acceptor and platelet derived growth factor, intensity of radioactivity intensity is stronger, and in conjunction with more, otherwise intensity of radioactivity intensity is more weak, in conjunction with fewer.Result shows, with platelet derived growth factor antagonism polypeptide concentration increase, is combined with platelet derived growth factor and increases gradually, illustrate and platelet derived growth factor binding ability constantly reduce with the increase of drug level.
Embodiment 2
Platelet derived growth factor antagonism polypeptide is to the growth of cultured tumor cells in vitro and survival IC50.
Adopt MTT colorimetry.By the HepG2 cell of logarithmic growth, with 1.0 × 10
5add in 96 well culture plates, cultivate 24h, experimental port, positive drug control hole add Experimental agents platelet derived growth factor antagonism polypeptide (the raw work synthesis in Shanghai) and the positive control medicine vincristine(VCR) of different concns respectively; Blank group adds the solvent of same volume.Five multiple holes are established in every hole, cultivate 48h, respectively 0h, 2h, 8h, 14h, 20h, 24h, 36h, the every hole of 48h adds MTT, after effect 4h, add DMSO, hatch 30min, absorbance A value is measured, by formula growth of tumour cell inhibiting rate=(1-experimental group light absorption value/control group light absorption value) × 100% at microplate reader 620nm place.The IC50 calculating Experimental agents is 65.32 μMs.
Embodiment 3
With vigor in the body of tumor model detection platelet derived growth factor antagonism polypeptide.
Set up HepG2 tumor model, positive control medicine vincristine(VCR); Blank group adds the solvent of same volume, and experimental group polypeptide (the raw work synthesis in Shanghai) establishes 3 dosage: 2.0,4.0,8.0 μMs/Kg.After 21 days, observe mouse survival quantity, calculate survival rate.Result shows, and platelet derived growth factor antagonism polypeptide (the raw work synthesis in Shanghai) can protect small white mouse effectively, and improve the survival rate of tumor-bearing mice, survival rate reaches 71.3%.
SEQUENCE LISTING
Pu Luoda bio tech ltd, <110> Suzhou
<120> platelet derived growth factor antagonism polypeptide and application thereof
<130>
<160> 1
<170> PatentIn version 3.3
<210> 1
<211> 21
<212> PRT
<213> artificial sequence
<400> 1
Met Lys Val Ser Ile Met Asp Lys Gly Arg Phe Ser Val Lys Thr Val
1 5 10 15
His Arg Gln Ala Pro
20
Claims (2)
1. platelet derived growth factor antagonism polypeptide, is characterized in that its sequence YCRCADQDTWLGHTRISETI.
2. platelet derived growth factor antagonism polypeptide is preparing the application in prevention and therapy liver-cancer medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510157258.7A CN104693284A (en) | 2015-04-06 | 2015-04-06 | Platelet-derived-growth-factor antagonistic polypeptide and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510157258.7A CN104693284A (en) | 2015-04-06 | 2015-04-06 | Platelet-derived-growth-factor antagonistic polypeptide and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104693284A true CN104693284A (en) | 2015-06-10 |
Family
ID=53340871
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510157258.7A Withdrawn CN104693284A (en) | 2015-04-06 | 2015-04-06 | Platelet-derived-growth-factor antagonistic polypeptide and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104693284A (en) |
-
2015
- 2015-04-06 CN CN201510157258.7A patent/CN104693284A/en not_active Withdrawn
Non-Patent Citations (3)
| Title |
|---|
| CARL-HENRIK HELDIN: "Development and possible clinical use of antagonists for PDGF and TGF-β", 《UPSALA JOURNAL OF MEDICAL SCIENCES》 * |
| 李代洪等: "血小板衍生生长因子受体（PDGFR）抑制剂的研究进展", 《肿瘤药学》 * |
| 谢峰等: "原发性肝癌分子靶向治疗临床进展", 《中华肝胆外科杂志》 * |
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|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20150610 |