CN104017056A - Protein ST2 inhibitor polypeptide and application thereof - Google Patents
Protein ST2 inhibitor polypeptide and application thereof Download PDFInfo
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- CN104017056A CN104017056A CN201410293554.5A CN201410293554A CN104017056A CN 104017056 A CN104017056 A CN 104017056A CN 201410293554 A CN201410293554 A CN 201410293554A CN 104017056 A CN104017056 A CN 104017056A
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Abstract
The invention relates to the field of drugs and particularly relates to a polypeptide capable of inhibiting the expression of protein ST2 and treating uterine cancer. The sequence of the polypeptide is RNLHGLRRHTVR and is a bran-new sequence; the polypeptide can be used for inhibiting the proliferation of uterine cancer cells Hela in an in-vitro manner and treating the uterine cancer; shown by in-vivo tumor-bearing model experiments, the expression of tumor protein ST2 can be inhibited, and the survival rate of mice can be increased, so that the polypeptide has a potential value of new drug development.
Description
Technical field
The present invention relates to ST2 protein inhibitor polypeptide and application thereof, be specifically related to have and suppress ST2 protein expression, treat the polypeptide of uterus carcinoma.
Background technology
Uterus carcinoma cervical cancer is one of modal malignant tumour of gynaecology.Treat half a year to perform the operation as major-minor, taking medicines such as radiotherapy, chemotherapy, progesterone estrogen antagonists as auxiliary.But operation is difficult to excise completely cancerous tissue and subclinical focus.Next is exactly chemicotherapy, but the equal normal tissue organ of these two kinds of therapeutic modalities has obvious side reaction, and the damage that further improves curative effect and reduce normal tissue is the problem that is worth research.At present biological targeting treatment tumour is very promising, and targeted therapy is for blocking certain or multiple signal path in tumour generating process, reaches the object for the treatment of tumour.
Medical circle also can not determine that what reason causes uterus carcinoma up to now, it is generally acknowledged it may is that the intersection synergy of multinomial factor is caused, its risk factor has: the frequent or sexual life disorder of cervical erosion, sexual behaviour or ignore cleaning, ignore menstrual hygiene, sex partner's redundant prepuce and may having substantial connection with bleb two C-type virus Cs (HSV_2) and human papilloma (HPS) of sexual behaviour, even connects the inflammation-related such as venereal disease, Chlamydia infection.Blood of cancer patients lymphocyte is in the dominant state of Th2 type cell, and tumour cell itself is also in the dominant state of Th2, because Th1 cell is suppressed, cellular immune function can not activate effectively, antineoplastic immune ability declines, thereby be unfavorable for that body tissue, taking cellular immunization as main anti tumor immune response, makes the development of tumour cell existence.ST2 is more intense Th2 cell induction agent, a large amount of releases of Th2 cytokines in uterus carcinoma, facilitated Th0 cell to Th2 direction polarization, and Th2 polarization can produce a large amount of pro-inflammatory cytokines such as IL-6, causes and aggravated systemic inflammatory response.In addition, preponderate and be often accompanied by immunological tolerance at Th2 type cell, this has also facilitated uterine hemorrhage necrosis to increase the weight of.Delete the transmembrane ST2 acceptor (ST2L) of the uterus tumor of mouse and can lead the reduction of oncogenic growth and transfer, and increased the pro-inflammatory cytokine of cyclical level, NK cell and the CD8+T cell of activation.It is a raw important factor of uterus carcinoma that ST2 protein function raises.Therefore, suppressing ST2 protein expression, suppress uterus carcinoma development, is the novel targets for the treatment of uterus carcinoma.But, not yet have the medicine of the treatment uterus carcinoma of the ripe ST2 protein inhibitor polypeptide of exploitation
ST2 protein inhibitor polypeptide in this patent has proved in uterus carcinoma effective, has the prospect of developing in other tumor models.
Summary of the invention
goal of the invention
The invention provides brand-new sequence, this sequence suppresses ST2 protein expression, and uterus carcinoma is had to good curative effect.
technical scheme
ST2 protein inhibitor polypeptide, is characterized in that its sequence is RNLHGLRRHTVR.
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 polypeptide, is characterized in that effective dose is 10mg/kg.
The application of ST2 protein inhibitor polypeptide in treatment uterus carcinoma medicine.
beneficial effect
ST2 protein inhibitor polypeptide 2, this polypeptide has brand-new sequence, and this polypeptide can vitro inhibition uterus carcinoma cell Hela cell proliferation, treatment uterus carcinoma; Can suppress in vivo the tumour ST2 protein expression of lotus knurl model experiment, and can increase the survival rate of mouse, there is potential new drug development and be worth.
Embodiment
polypeptide of the present invention is synthetic by gill biochemistry (Shanghai)
Embodiment 1
Impact with tumor model detection ST2 protein inhibitor polypeptide on ST2 protein expression in tumour.
Set up people's uterus carcinoma cell Hela tumor model, positive control medicine vincristine(VCR); Blank group adds the solvent of same volume, and experimental group is established 3 dosage: 5,10,20 mg/Kg.After 21 days, put to death, get tumor tissues and carry out the experiment of ST2 protein immunization result, adopt Motic Images Advanced 3.2 image analyzers, under 200 times of mirrors, 5 visuals field of Continuous Observation are detected, and measure gray-scale value, represent the height of ST2 protein positive expression with gray-scale value, gray-scale value is less, illustrates that ST2 protein positive expression is lower; Gray-scale value is larger, illustrates that ST2 protein positive expression is higher.As a result, ST2 protein inhibitor polypeptide 2 has the effect that suppresses tumour ST2 protein expression.
Embodiment 2
The effect of ST2 protein inhibitor polypeptide to people's uterus carcinoma cell Hela propagation.
Adopt MTT colorimetry.By the Hela cell of logarithmic growth, add in 96 well culture plates with 1.0 × 105, cultivate 24h, experimental port, positive drug control wells add respectively Experimental agents ST2 protein inhibitor polypeptide 2 and the positive control medicine vincristine(VCR) of different concns; Blank group adds the solvent of same volume.Five multiple holes are established in every hole, cultivate 48h, add MTT in 0h, 2h, 8h, 14h, 20h, 24h, the every hole of 36h, 48h respectively, after effect 4h, add DMSO, hatch 30min, measure absorbance A value at microplate reader 620nm place, by formula growth of tumour cell inhibiting rate=(1-experimental group light absorption value/control group light absorption value) × 100%.Be 69.09% to the maximum proliferation inhibition rate of Hela.
Embodiment 3
The inhibition test of ST2 protein inhibitor polypeptide to human cervical carcinoma HeLa bare mouse different species Growth of Tumors Transplanted
The HeLa Cells strain of taking the logarithm vegetative period is prepared into 5 × 10 under aseptic condition
7/ ml cell suspension, is inoculated in nude mice right side armpit with 0.1ml subcutaneous.With vernier caliper measurement transplanted tumor in nude mice diameter, treat that tumor growth is to 100-200mm
3after by animal random packet.Use the method for measuring knurl footpath, dynamically observe the antitumous effect of tested polypeptide.The measurement number of times of diameter of tumor is to survey 1 time for every 2 days.Administering mode all adopts tail vein injection.Negative control group injection equivalent physiological saline, every day 1 time; Taxol group 10mg/kg, weekly administration 1 time; RhEndostatin group 2.5mg/kg, administration every day 1 time; High, normal, basic group of polypeptide is respectively with 20mg/kg, 10mg/kg, 5mg/kg, administration every day 1 time.After off-test, mouse is put to death, and operation strips knurl piece and weighs.
The restraining effect of table 1. polypeptide to human cervical carcinoma HeLa bare mouse different species Growth of Tumors Transplanted
Polypeptide shows human cervical carcinoma HeLa transplanted tumor in nude mice growth inhibition test result, compared with negative control group, polypeptide 20mg/kg group has the restraining effect of utmost point significance to the growth of human cervical carcinoma HeLa transplanted tumor, polypeptide 10mg/kg group has the restraining effect of significance to the growth of human cervical carcinoma HeLa transplanted tumor.Compared with positive controls taxol, polypeptide does not have a significant effect to the body weight of laboratory animal, has no obvious toxic side effects.
SEQUENCE LISTING
Pu Luoda bio tech ltd, <110> Suzhou
<120> ST2 protein inhibitor polypeptide and application thereof
<130>
<160> 1
<170> PatentIn version 3.3
<210> 1
<211> 12
<212> PRT
<213> artificial sequence
<400> 1
Arg Asn Leu His Gly Leu Arg Arg His Thr Val Arg
1 5 10
Claims (5)
1.ST2 protein inhibitor polypeptide, is characterized in that its sequence is RNLHGLRRHTVR.
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, is characterized in that, described composition is injection.
4. polypeptide as claimed in claim 1, is characterized in that effective dose is 10mg/kg.
5. the application of ST2 protein inhibitor polypeptide as claimed in claim 1 in treatment uterus carcinoma medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410293554.5A CN104017056B (en) | 2014-06-27 | 2014-06-27 | ST2 protein inhibitor polypeptide and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410293554.5A CN104017056B (en) | 2014-06-27 | 2014-06-27 | ST2 protein inhibitor polypeptide and application thereof |
Publications (2)
| Publication Number | Publication Date |
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| CN104017056A true CN104017056A (en) | 2014-09-03 |
| CN104017056B CN104017056B (en) | 2016-08-17 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201410293554.5A Active CN104017056B (en) | 2014-06-27 | 2014-06-27 | ST2 protein inhibitor polypeptide and application thereof |
Country Status (1)
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| CN (1) | CN104017056B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001070817A1 (en) * | 2000-03-21 | 2001-09-27 | Medical & Biological Laboratories Co., Ltd. | Monoclonal antibody and method and kit for the immunoassay of soluble human st2 with the use of the same |
| CN103796669A (en) * | 2011-07-18 | 2014-05-14 | 重症监护诊断股份有限公司 | Methods of treating cardiovascular diseases and predicting the efficacy of exercise therapy |
-
2014
- 2014-06-27 CN CN201410293554.5A patent/CN104017056B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001070817A1 (en) * | 2000-03-21 | 2001-09-27 | Medical & Biological Laboratories Co., Ltd. | Monoclonal antibody and method and kit for the immunoassay of soluble human st2 with the use of the same |
| CN103796669A (en) * | 2011-07-18 | 2014-05-14 | 重症监护诊断股份有限公司 | Methods of treating cardiovascular diseases and predicting the efficacy of exercise therapy |
Non-Patent Citations (2)
| Title |
|---|
| MARIJA MILOVANOVIC ET AL.: "IL-33/ST2 axis in inflammation and immunopathology", 《IMMUNOL RES》 * |
| 白芳芸等: "ST2蛋白在胃癌中的表达及意义", 《中国现代医学杂志》 * |
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| Publication number | Publication date |
|---|---|
| CN104017056B (en) | 2016-08-17 |
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| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| CB03 | Change of inventor or designer information |
Inventor after: Pei Donghong Inventor before: Luo Ruixue |
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| COR | Change of bibliographic data | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20160701 Address after: 100097 Beijing city Haidian District landianchang Road No. 2 Building No. 2 hospital 6 floor 3 unit (C) 7G Applicant after: Biotechnology (Beijing) Co., Ltd. Address before: High tech Zone Suzhou city Jiangsu province 215000 Chuk Yuen Road No. 209 Applicant before: Suzhou Pu Luo Da Biotechnology Co., Ltd. |
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