CN105198965A - VEGFR2 blocker polypeptide and application thereof - Google Patents
VEGFR2 blocker polypeptide and application thereof Download PDFInfo
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- CN105198965A CN105198965A CN201510710960.1A CN201510710960A CN105198965A CN 105198965 A CN105198965 A CN 105198965A CN 201510710960 A CN201510710960 A CN 201510710960A CN 105198965 A CN105198965 A CN 105198965A
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- polypeptide
- vegfr2
- ovarian cancer
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Abstract
The invention relates to the medicine field, and particularly relates to a polypeptide capable of inhibiting interleukin-33 and treating ovarian cancer. The polypeptide has the sequence of ADHEFFIMTSYPPWRGD which is a brand new sequence, can block VEGF from being combined with VEGFR2, thereby affecting conduction of a VEGF downstream signal and achieving the antitumor purpose. Ovarian cancer in-vivo and in-vitro models are adopted for verifying that the polypeptide can effectively inhibit tumor proliferation and growth, can be used as an effective antitumor drug candidate and provides a new choice for development of new-generation antitumor drugs.
Description
Technical field:
The present invention relates to pharmaceutical field, be specifically related to the combination for blocking VEGF R2, the VEGFR2 blocker polypeptide for the treatment of ovarian cancer.
Background technology:
Malignant tumor of ovary is one of common malignant tumour of female sex organ, and sickness rate is only second to cervical cancer and carcinoma of uterine body and arranges the 3rd, residence.But ovarian epithelium mortality of carcinoma accounts for the first place of all kinds of gynecological tumor, serious threat is caused to women's life.Because the fetal development of ovary, anatomic tissue and endocrine function are more complicated, early symptom is not true to type, the organization type of preoperative identification of ovarian tumour and good pernicious quite difficulty.The most common with epithelial cancer in malignant tumor of ovary, be secondly malignant germ cell tumors.What find in epithelial ovarian cancer corrective surgery that tumour is confined to ovary only accounts for 30%, and great majority are diffused into uterus, bilateral annex, greater omentum and each organ of pelvic cavity.Current methods for the treatment of has:. operative treatment, chemotherapy, radiotherapy etc.Because malignant tumor of ovary especially epithelial cancer spreads very early, during operation, majority of cases can not remove focus, and the effect of radiotherapy and application also very limited, therefore systemic chemotherapy is an important auxiliary treating method.Especially malignant germ cell tumors, specification chemotherapy can significantly improve survival.Some end-stage patients, after chemotherapy, lump can reduce, and creates favorable conditions for satisfaction during operation subtracts knurl.But antitumor drug existence makes patient's immunocompromised, the side effects such as hair loss, vomiting, weight loss, limit its application.How to find efficient, the low ovarian cancer resistance medicament of side effect becomes a difficult problem urgently to be resolved hurrily.
The growth of tumour be unable to do without the new life of blood vessel and the stimulation of various somatomedin and release, and Tumor suppression new vessel may become a kind of effective ways for the treatment of tumour.Vascular endothelial growth factor (Vascularendothelialgrowthfactor, VEGF) high expression level and the formation of noumenal tumour and shift closely related, VEGF by with the specific receptors (Vascularendothelialgrowthfactorreceptor on endothelial cellular membrane, VEGFR) combine in the born of the same parents of activation signal conduction and have high expression level, and expression level is very low in the one-tenth person of health does not even express.VEGFR2 can promote vascular endothelial cell proliferation, migration and increase capillary permeability.The mitotic division of tumor vascular endothelial cell and the perviousness of tumor-microvessel are mainly occurred by the interaction of VEGF and VEGFR2.Therefore, VEGFR2 blocker, can effectively suppress VEGF and VEGFR2 to combine, and then effectively Tumor suppression is bred, and migration reaches the object of Tumor suppression growth.
Summary of the invention:
The invention provides brand-new sequence, this sequence blocking VEGF R2, in conjunction with VEGF, has good curative effect to ovarian cancer.
Technical scheme
VEGFR2 blocker polypeptide, is characterized in that its sequence is ADHEFFIMTSYPPWRGD.
A kind of pharmaceutical composition, is characterized in that it comprises polypeptide and more than one pharmaceutically acceptable vehicle, weighting agent, tackiness agent, lubricant, disintegrating agent or stablizer as claimed in claim 1.
Described pharmaceutical composition, is characterized in that, described composition is injection.
Described VEGFR2 blocker polypeptide, is characterized in that effective dose is 10mg/kg.
Described VEGFR2 blocker polypeptide, the application in treatment ovarian cancer.
Beneficial outcomes:
VEGFR2 blocker polypeptide 1 sequence A DHEFFIMTSYPPWRGD in the present invention, can blocking VEGF in conjunction with VEGFR2, and then affect VEGF downstream signal conduction, realize antitumor object.The present invention adopts the modelling verification of ovarian cancer inside and outside, and it can effective Tumor suppression propagation, and growth, can as effective antitumour drug candidate, for Development of New Generation antitumor drug provides new selection.
Embodiment
The present invention relates to polypeptide (ADHEFFIMTSYPPWRGD) to be synthesized by gill biochemistry (Shanghai).Human ovarian cancer SK-OV-3 is purchased from Shanghai cell biological institute of Chinese Academy of Sciences cell bank.
Embodiment 1
The effect that VEGFR2 blocker polypeptide is bred Proliferation of Human Ovarian Cell SK-OV-3
Adopt MTT colorimetry:
1, cell cultures: abortion syndrome SK-OV-3 with containing McCoy ' the s5A substratum of 10% foetal calf serum, 37 DEG C, 5%CO2, to cultivate under saturated humidity condition, be epithelial cell type, adherent growth.Every 2 ~ 3 days with 0.25% pancreatin and 0.02%EDTA conventional digestion, 1:3 ~ 1:6 Secondary Culture.
2, by the SK-OV-3 cell of logarithmic growth, add in 96 well culture plates with 1.0 × 105, cultivate 24h, experimental port, positive drug control hole add Experimental agents VEGFR2 blocker polypeptide 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, and cultivate 48h, every hole 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 0.41 μM.And positive control medicine vincristine(VCR) 0.39 μM, both do not have significant difference, illustrate that polypeptide of the present invention has and suppress human ovarian cancer effect.
The inhibition test that embodiment 2VEGFR2 blocker polypeptide grows Proliferation of Human Ovarian Cell SK-OV-3 nude mouse xenograft tumor
The Proliferation of Human Ovarian Cell SK-OV-3 cell strain of taking the logarithm vegetative period, is aseptically prepared into 5 × 10
7/ ml cell suspension, is inoculated in armpit on the right side of nude mice with 0.1ml subcutaneous.With vernier caliper measurement transplanted tumor in nude mice diameter, treat that tumor growth is to 70-100mm
3after by animal random packet.Use the method measuring knurl footpath, dynamically observe the antitumous effect of tested polypeptide.The pendulous frequency of diameter of tumor is survey 1 time for every 2 days.Administering mode all adopts tail vein injection.Negative control group injection normal saline, every day 1 time; Taxol group 10mg/kg, Per-Hop behavior 1 time; High, normal, basic group of polypeptide respectively with 20mg/kg, 10mg/kg, 5mg/kg, administration every day 1 time.Administration 21d.After off-test, sacrifice, operation strips knurl block and weighs.
The restraining effect that table 1 polypeptide grows Proliferation of Human Ovarian Cell SK-OV-3 nude mouse xenograft tumor
Polypeptide shows Proliferation of Human Ovarian Cell SK-OV-3 transplanted tumor in nude mice growth inhibition test result, compared with negative control group, polypeptide 20mg/kg, 10mg/kg and 5mg/kg group all has the restraining effect of pole significance to the growth of Proliferation of Human Ovarian Cell SK-OV-3 transplanted tumor.20mg/kg, 10mg/kg and 5mg/kg are compared with positive controls taxol, and the body weight of polypeptide to laboratory animal does not have a significant effect, and has no obvious toxic side effects, and survival rate improves.
SEQUENCELISTING
Pu Luoda bio tech ltd, <110> Suzhou
<120> VEGFR2 blocker polypeptide and application thereof
<130>
<160>1
<170>PatentInversion3.3
<210>1
<211>17
<212>PRT
<213> artificial sequence
<400>1
AlaAspHisGluPhePheIleMetThrSerTyrProProTrpArgGly
151015
Asp
Claims (5)
1.VEGFR2 blocker polypeptide, is characterized in that its sequence is ADHEFFIMTSYPPWRGD.
2. a pharmaceutical composition, is characterized in that it comprises polypeptide and more than one pharmaceutically acceptable vehicle, weighting agent, tackiness agent, lubricant, disintegrating agent or stablizer as claimed in claim 1.
3. pharmaceutical composition as claimed in claim 2, it is characterized in that, described composition is injection.
4. VEGFR2 blocker polypeptide as claimed in claim 1, is characterized in that effective dose is 10mg/kg.
5. VEGFR2 blocker polypeptide as claimed in claim 1, the application in treatment ovarian cancer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510710960.1A CN105198965A (en) | 2015-10-28 | 2015-10-28 | VEGFR2 blocker polypeptide and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510710960.1A CN105198965A (en) | 2015-10-28 | 2015-10-28 | VEGFR2 blocker polypeptide and application thereof |
Publications (1)
| Publication Number | Publication Date |
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| CN105198965A true CN105198965A (en) | 2015-12-30 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| CN201510710960.1A Pending CN105198965A (en) | 2015-10-28 | 2015-10-28 | VEGFR2 blocker polypeptide and application thereof |
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| CN (1) | CN105198965A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102127161A (en) * | 2010-12-16 | 2011-07-20 | 何明忠 | Antitumor polypeptide and application thereof |
| CN102488890A (en) * | 2011-12-27 | 2012-06-13 | 中国药科大学 | Application of integrin blocker polypeptide AP25 in preparation of medicines for treating tumor |
| CN102850443A (en) * | 2011-12-27 | 2013-01-02 | 中国药科大学 | Integrin blocker polypeptides and application thereof |
-
2015
- 2015-10-28 CN CN201510710960.1A patent/CN105198965A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102127161A (en) * | 2010-12-16 | 2011-07-20 | 何明忠 | Antitumor polypeptide and application thereof |
| CN102488890A (en) * | 2011-12-27 | 2012-06-13 | 中国药科大学 | Application of integrin blocker polypeptide AP25 in preparation of medicines for treating tumor |
| CN102850443A (en) * | 2011-12-27 | 2013-01-02 | 中国药科大学 | Integrin blocker polypeptides and application thereof |
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| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20151230 |
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| WD01 | Invention patent application deemed withdrawn after publication |