CN104693282A - Angiostatin activator polypeptide and application thereof - Google Patents
Angiostatin activator polypeptide and application thereof Download PDFInfo
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- CN104693282A CN104693282A CN201510157246.4A CN201510157246A CN104693282A CN 104693282 A CN104693282 A CN 104693282A CN 201510157246 A CN201510157246 A CN 201510157246A CN 104693282 A CN104693282 A CN 104693282A
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- Prior art keywords
- angiostatin
- polypeptide
- activator polypeptide
- application
- tumor
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Abstract
The invention relates to the field of medicines, in particular to polypeptide for activating angiostatin and treating cancers. The sequence of the polypeptide is NYTPANTPFDFHHSLEHG which is brand new, the polypeptide can activate angiostatin and restrain vascular endothelial cell proliferation in vitro, 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
The present invention relates to angiostatin activator polypeptide and application thereof, be specifically related to that there is activating vessels chalone, the polypeptide for the treatment of malignant tumour.
Background technology
Folkman in 1971 proposes growth and metastasis of tumours and relies on new vessel generation.And after thinking that solid tumor is formed, its development can be divided into without blood vessel phase and two stages of blood vessel phase.Without the blood vessel phase, the existence of minimal neoplastic relies on interstitial disperse blood supply around, and linearly, tumour is limited within 1mm ~ 2mm the speed of growth, and oncocyte number is less than 10
5~ 10
6individual, force tumour to be in " dormant state "; Intravasation after date, tumor tissues is the blood supply of perfusion property, and the exponentially property growth of knurl body, can increase 1. 6 ten thousand times after 2 weeks.New vessel not only provides nutrition required for tumour and oxygen, gets rid of meta-bolites, and is the approach of distant metastasis.Therefore, block tumor angiogenesis and just may stop growth and metastasis of tumours, anti-new vessel therapy also one of means becoming oncotherapy.
Angiostatin is the hydrolysate of proplasmin, has stronger angiogenesis inhibiting activity.Large quantity research confirms that angiostatin can suppress growth and the migration of endotheliocyte in vitro, new vessel can be suppressed to be formed in vivo in test, thus inducing apoptosis of tumour cell, Tumor suppression grows, and tumour is in " dormant state ".
Therefore, activating vessels chalone, can effectively suppress vascular endothelial cell proliferation in body, the growth of Tumor suppression.Thus, reach the effect for the treatment of tumour.
At present, do not have the angiostatin activator polypeptide of ripe exploitation to come out, be used for the treatment of malignant tumour.
Angiostatin activator polypeptide in this patent proved before the treatment in row gland cancer effectively, there is the prospect developed in other tumor models.
Summary of the invention
goal of the invention
The invention provides brand-new sequence, this sequence is angiostatin activator polypeptide, has good curative effect to malignant tumour.
technical scheme
angiostatin activator polypeptide, is characterized in that its sequence is NYTPANTPFDFHHSLEHG.
Angiostatin activator polypeptide treatment malignant tumour, as the application in prostate cancer medicine.
beneficial effect
Utilize solid-phase synthesis chemosynthesis angiostatin activator polypeptide, this polypeptide has brand-new sequence, and this polypeptide can be hydrolyzed by external promotion proplasmin, and treatment malignant tumour, as prostate cancer.The angiostatin activator polypeptide that we find can suppress vascular endothelial cell proliferation vigor simultaneously, and improves tumor-bearing mice survival rate in testing in vivo, has potential new drug development value.
Embodiment
Embodiment 1
Angiostatin activator polypeptide is to the activity of extracorporeal hydrolysis proplasmin.
Adopt the former hydrolysate of ELISA method detection fibers plasmin---angiostatin.Be substrate by the Tryptase of the 1mg/ml of 1ml, in substrate solution, add 0.1 respectively, 0.2, the angiostatin activator polypeptide (the raw work synthesis in Shanghai) of 0.3nM and positive control drug metalloprotease 1.0nM, at 37 DEG C, after reaction 5min, centrifugal, get supernatant, with the content of solution Effect of Angiostatin after ELISA method reaction, result shows, 5,10, the angiostatin that produces of the angiostatin activator polypeptide of 20ng and metalloprotease is respectively 243.43,342.87,475.66 μMs.
Embodiment 2
Angiostatin activator polypeptide is to the growth of vitro culture human vascular endothelial and survival IC50.
Adopt MTT colorimetry.By the human vascular endothelial HUVEC of logarithmic growth, with 1.0 × 10
5add in 96 well culture plates, cultivate 24h, experimental port, positive drug control hole add Experimental agents angiostatin activator polypeptide (the raw work synthesis in Shanghai) and the positive control medicine taxol 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 HUVEC growth inhibition ratio=(1-experimental group light absorption value/control group light absorption value) × 100% at microplate reader 620nm place.The IC50 calculating Experimental agents is 8.08 μMs.
Embodiment 3
With vigor in the body of tumor model detection angiostatin activator polypeptide.
Set up tumor model of prostate cancer, positive control medicine taxol; Blank group adds the solvent of same volume, and experimental group polypeptide (the raw work synthesis in Shanghai) establishes 3 dosage: 0.75,1.5,3 mg/Kg.After 21 days, observe mouse survival quantity, calculate survival rate.Result shows, and angiostatin activator polypeptide can protect small white mouse effectively, and improve the survival rate of tumor-bearing mice, survival rate reaches 91.0%.
SEQUENCE LISTING
Pu Luoda bio tech ltd, <110> Suzhou
<120> is about angiostatin activator polypeptide and application thereof
<130>
<160> 1
<170> PatentIn version 3.3
<210> 1
<211> 18
<212> PRT
<213> artificial sequence
<400> 1
Asn Tyr Thr Pro Ala Asn Thr Pro Phe Asp Phe His His Ser Leu Glu
1 5 10 15
His Gly
Claims (3)
1. angiostatin activator polypeptide, is characterized in that its sequence is NYTPANTPFDFHHSLEHG.
2. the application of angiostatin activator polypeptide in tumor as claimed in claim 1.
3. the application of angiostatin activator polypeptide as claimed in claim 2 before the treatment in row gland cancer medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510157246.4A CN104693282A (en) | 2015-04-06 | 2015-04-06 | Angiostatin activator polypeptide and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510157246.4A CN104693282A (en) | 2015-04-06 | 2015-04-06 | Angiostatin activator polypeptide and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104693282A true CN104693282A (en) | 2015-06-10 |
Family
ID=53340869
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510157246.4A Pending CN104693282A (en) | 2015-04-06 | 2015-04-06 | Angiostatin activator polypeptide and application thereof |
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| CN (1) | CN104693282A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105039293A (en) * | 2015-08-20 | 2015-11-11 | 倪勤华 | Angiostatin activator polypeptide |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1857206A (en) * | 2006-03-06 | 2006-11-08 | 济南帅华医药科技有限公司 | Slow released anticancer injection containing blood vessel inhibitor |
| CN1861047A (en) * | 2006-03-06 | 2006-11-15 | 济南帅华医药科技有限公司 | Slow-releasing injection contg. vasoinhibitor and potentiator type anticarcinogen |
-
2015
- 2015-04-06 CN CN201510157246.4A patent/CN104693282A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1857206A (en) * | 2006-03-06 | 2006-11-08 | 济南帅华医药科技有限公司 | Slow released anticancer injection containing blood vessel inhibitor |
| CN1861047A (en) * | 2006-03-06 | 2006-11-15 | 济南帅华医药科技有限公司 | Slow-releasing injection contg. vasoinhibitor and potentiator type anticarcinogen |
Non-Patent Citations (2)
| Title |
|---|
| 王文慧: "从噬菌体肽库中筛选具有抗前列腺癌功能的新型FGF8b结合肽", <中国优秀硕士学位论文全文数据库> * |
| 邵秋菊等: "血管生成抑制素在实体瘤治疗中的研究进展", <肿瘤防治杂志> * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105039293A (en) * | 2015-08-20 | 2015-11-11 | 倪勤华 | Angiostatin activator polypeptide |
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| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20150610 |