CN104693283A - Angiostatin activating agent polypeptide and application thereof - Google Patents
Angiostatin activating agent polypeptide and application thereof Download PDFInfo
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- CN104693283A CN104693283A CN201510157247.9A CN201510157247A CN104693283A CN 104693283 A CN104693283 A CN 104693283A CN 201510157247 A CN201510157247 A CN 201510157247A CN 104693283 A CN104693283 A CN 104693283A
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- angiostatin
- polypeptide
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- tumor
- activator polypeptide
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Abstract
The invention relates to the field of drugs, in particular to a polypeptide having functions of activating angiostatin and treating malignant tumor. The sequence of the polypeptide is a novel sequence of DEQWLMYPLFHSGLF, and the polypeptide can activate angiostatin in vitro, restrain vascular endothelial cells from proliferating, and improve the survival rate of tumor-bearing mice in vivo tests, thereby having potential development values of new drugs.
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 DEQWLMYPLFHSGLF.
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 5 respectively, 10, the angiostatin activator polypeptide (the raw work synthesis in Shanghai) of 20ng and positive control drug metalloprotease 60ng, 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 105.69,489.47,1547.12 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, add in 96 well culture plates with 1.0 × 105, 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 44.32 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 76.3%.
SEQUENCE LISTING
Pu Luoda bio tech ltd, <110> Suzhou
<120> angiostatin activator polypeptide and application thereof
<130>
<160> 1
<170> PatentIn version 3.3
<210> 1
<211> 15
<212> PRT
<213> artificial sequence
<400> 1
Asp Glu Gln Trp Leu Met Tyr Pro Leu Phe His Ser Gly Leu Phe
1 5 10 15
Claims (3)
1. angiostatin activator polypeptide, is characterized in that its sequence is DEQWLMYPLFHSGLF.
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 |
|---|---|---|---|
| CN201510157247.9A CN104693283A (en) | 2015-04-06 | 2015-04-06 | Angiostatin activating agent polypeptide and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510157247.9A CN104693283A (en) | 2015-04-06 | 2015-04-06 | Angiostatin activating agent polypeptide and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104693283A true CN104693283A (en) | 2015-06-10 |
Family
ID=53340870
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510157247.9A Pending CN104693283A (en) | 2015-04-06 | 2015-04-06 | Angiostatin activating agent polypeptide and application thereof |
Country Status (1)
| Country | Link |
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| CN (1) | CN104693283A (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 (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1680430A (en) * | 2005-01-12 | 2005-10-12 | 复旦大学 | Mimic peptide of human plasminogen activator and preparation thereof |
-
2015
- 2015-04-06 CN CN201510157247.9A patent/CN104693283A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1680430A (en) * | 2005-01-12 | 2005-10-12 | 复旦大学 | Mimic peptide of human plasminogen activator and preparation thereof |
Non-Patent Citations (3)
| Title |
|---|
| H H RASHID等: "Anti-angiogenic and cytotoxic targeted systemic therapy for high-risk prostate cancer", 《UROLOGIC ONCOLOGY:SEMINARS AND ORIGINAL INVESTIGATIONS》 * |
| S. GATELY等: "The mechanism of cancer-mediated conversion of plasminogen to the angiogenesis inhibitor angiostatin", 《PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES》 * |
| 吴景文等: "血管抑素与肿瘤的抗血管生成治疗", 《国外医学肿瘤学分册》 * |
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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| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20150610 |
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| RJ01 | Rejection of invention patent application after publication |