CN104017056B - ST2 protein inhibitor polypeptide and application thereof - Google Patents
ST2 protein inhibitor polypeptide and application thereof Download PDFInfo
- Publication number
- CN104017056B CN104017056B CN201410293554.5A CN201410293554A CN104017056B CN 104017056 B CN104017056 B CN 104017056B CN 201410293554 A CN201410293554 A CN 201410293554A CN 104017056 B CN104017056 B CN 104017056B
- Authority
- CN
- China
- Prior art keywords
- polypeptide
- tumor
- protein inhibitor
- uterus carcinoma
- inhibitor polypeptide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Abstract
The present invention relates to drug world, be specifically related to that there is suppression ST2 protein expression, the polypeptide for the treatment of uterus carcinoma.Its sequence be RNLHGLRRHTVR be brand-new sequence, this polypeptide can vitro inhibition uterine cancer cells Hela cell proliferation, treat uterus carcinoma；Can suppress the tumor ST2 protein expression of lotus tumor model experiment in vivo, and the survival rate of mice can be added, there is potential new drug development value.
Description
Technical field
The present invention relates to ST2 protein inhibitor polypeptide and application thereof, be specifically related to that there is suppression ST2 protein expression, treatment
The polypeptide of uterus carcinoma.
Background technology
Uterus carcinoma cervical cancer is one of modal malignant tumor of gynecological.Treatment half a year with operation for major-minor, with radiate
The medicines such as treatment, chemotherapy, progesterone estrogen antagonist are auxiliary.But operation is difficult to excise cancerous tissue and subclinical focus completely.
Next is exactly chemicotherapy, but both therapeutic modalities equal normal tissue organ has obvious side reaction, improves curative effect further
And the damage reducing normal tissue is the problem being worth research.Biological target therapy tumor is the most promising at present, target
It is for tumor generating process blocks certain or multiple signal path to treatment, reaches to treat the purpose of tumor.
Medical circle also not can be determined that what reason causes uterus carcinoma up to now, it is considered that is probably multinomial factor
Intersect caused by synergism, its risk factor has: cervical erosion, sexual behaviour are frequently or sexual life is disorderly or ignore
The cleaning of sexual behaviour, ignore menstrual hygiene, sex partner redundant prepuce and may be with herpes two type virus (HSV_2) and people's nipple
Tumor (HPS) has substantial connection, even connects the inflammation-related such as sexually transmitted disease (STD), Chlamydia infection.Blood of cancer patients lymphocyte is in
The dominant state of Th2 type cell, and tumor cell itself is also at the dominant state of Th2, owing to Th1 cell is subject to
To suppression, cellular immune function can not activate effectively, and antineoplastic immune ability declines, thus is unfavorable for that body tissue is with cell
Immunity is main anti tumor immune response, makes tumor cell existence develop.ST2 is stronger Th2 cell induction
Agent, a large amount of releases of Th2 cytokines in uterus carcinoma, facilitate Th0 cell to Th2 direction polarization, and Th2
Polarization can produce again the proinflammatory cytokine of substantial amounts of such as IL-6, causes and exacerbates systemic inflammatory response.Additionally,
Th2 type cell is preponderated often along with immunologic tolerance, and this has also contributed to metrorrhagia necrosis and has increased the weight of.Delete the uterus of mice
Transmembrane ST2 receptor (ST2L) of tumor may result in the growth of tumor and the reduction of transfer, and adds the rush of cyclical level
Inflammatory cytokine, the NK cell of activation and CD8+T cell.It is that raw one of uterus carcinoma is important that ST2 protein function raises
Factor.Therefore, suppressing ST2 protein expression, suppression uterus carcinoma development, is the novel targets for the treatment of uterus carcinoma.But, not yet have exploitation
The medicine of the treatment uterus carcinoma of ripe ST2 protein inhibitor polypeptide
ST2 protein inhibitor polypeptide in this patent is proved in uterus carcinoma effectively, to be had in other tumor models
The prospect of exploitation.
Summary of the invention
Goal of the invention
The present invention provides brand-new sequence, this sequence suppression ST2 protein expression, has good curative effect to uterus carcinoma.
Technical scheme
ST2 protein inhibitor polypeptide, it is characterised in that its sequence is RNLHGLRRHTVR.
A kind of pharmaceutical composition, it is characterised in that it comprises polypeptide as claimed in claim 1 and pharmaceutically may be used with more than one
Excipient, filler, binding agent, lubricant, disintegrating agent or the stabilizer accepted.
Described pharmaceutical composition, it is characterised in that described compositions is injection.
Described polypeptide, it is characterised in that effective dose is 10mg/kg.
The application in treatment uterus carcinoma medicine of the ST2 protein inhibitor polypeptide.
Beneficial effect
ST2 protein inhibitor polypeptide 2, this polypeptide has brand-new sequence, and this polypeptide can vitro inhibition uterine cancer cells
Hela cell proliferation, treats uterus carcinoma；The tumor ST2 protein expression of lotus tumor model experiment can be suppressed in vivo, and can increase
The survival rate of mice, has a potential new drug development value.
Detailed description of the invention
Polypeptide of the present invention is by gill biochemical (Shanghai) synthesis
Embodiment 1
With tumor model detection ST2 protein inhibitor polypeptide on the impact of ST2 protein expression in tumor.
Set up people's uterine cancer cells Hela tumor model, positive control medicine vincristine；Blank group adds same volume
Solvent, experimental group sets 3 dosage: 5,10,20 mg/Kg.After 21 days, put to death, take tumor tissues and carry out ST2 protein immunization knot
Fruit is tested, and uses Motic Images Advanced 3.2 image analyzer, 5 visual field inspections of Continuous Observation under 200 times of mirrors
Surveying, measure gray value, represent the height of ST2 protein positive expression with gray value, gray value is the least, and ST2 protein positive table is described
Reach the lowest；Gray value is the biggest, illustrates that ST2 protein positive expression is the highest.As a result, ST2 protein inhibitor polypeptide 2 has suppression tumor
The effect of ST2 protein expression.
Embodiment 2
The effect that people uterine cancer cells Hela is bred by ST2 protein inhibitor polypeptide.
Use MTT colorimetry.By the Hela cell of logarithmic growth, add in 96 well culture plates with 1.0 × 105, training
Supporting 24h, experimental port, positive drug control hole are separately added into Experimental agents ST2 protein inhibitor polypeptide 2 and the sun of variable concentrations
Property control drug vincristine；Blank group adds the solvent of same volume.Every hole sets five multiple holes, cultivates 48h, respectively 0h,
The every hole of 2h, 8h, 14h, 20h, 24h, 36h, 48h adds MTT, after effect 4h, adds DMSO, hatches 30min, in microplate reader
Absorbance A value is measured, by formula growth of tumour cell suppression ratio=(1-experimental group light absorption value/matched group extinction at 620nm
Value) × 100%.Maximum proliferation inhibition rate to Hela is 69.09%.
Embodiment 3
The inhibition test that human cervical carcinoma's HeLa nude mouse xenograft tumor is grown by ST2 protein inhibitor polypeptide
Take the logarithm the HeLa Cells strain of trophophase, be aseptically prepared as 5 × 107/ ml cell suspension,
It is inoculated in axillary fossa on the right side of nude mice subcutaneous with 0.1ml.With vernier caliper measurement transplanted tumor in nude mice diameter, treat that tumor growth is to 100-
200mm3After by animal random packet.Use the method measuring tumor footpath, dynamically observe the antitumous effect of tested polypeptide.Tumor is straight
The pendulous frequency in footpath is to survey 1 time for every 2 days.Administering mode all uses tail vein injection.Negative control group injection normal saline,
Every day 1 time；Paclitaxel group 10mg/kg, Per-Hop behavior 1 time；RhEndostatin group 2.5mg/kg, is administered once daily；The high, normal, basic component of polypeptide
Not with 20mg/kg, 10mg/kg, 5mg/kg, it is administered once daily.After off-test, sacrifice, operation strips tumor mass and weighs.
The inhibitory action that human cervical carcinoma's HeLa nude mouse xenograft tumor is grown by table 1. polypeptide
Human cervical carcinoma's HeLa transplanted tumor in nude mice growth inhibition test result is shown by polypeptide, compared with negative control group, many
Peptide 20mg/kg group has the inhibitory action of pole significance to the growth of human cervical carcinoma's HeLa transplanted tumor, and polypeptide 10mg/kg group is to people palace
The growth of neck cancer HeLa transplanted tumor has the inhibitory action of significance.Compared with positive controls paclitaxel, polypeptide is to laboratory animal
Body weight have not significant impact, have no obvious toxicity.
SEQUENCE LISTING
<110>Suzhou Pu Luoda bio tech ltd
<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, it is characterised in that its sequence is RNLHGLRRHTVR.
2. a pharmaceutical composition, it is characterised in that it comprises polypeptide as claimed in claim 1 and pharmaceutically can connect with more than one
Excipient, filler, binding agent, lubricant, disintegrating agent or the stabilizer being subject to.
3. pharmaceutical composition as claimed in claim 2, it is characterised in that described compositions is injection.
4. polypeptide as claimed in claim 1, it is characterised in that effective dose is 10mg/kg.
5. the ST2 protein inhibitor polypeptide as claimed in claim 1 application in preparation 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 |
|---|---|
| CN104017056A CN104017056A (en) | 2014-09-03 |
| CN104017056B true CN104017056B (en) | 2016-08-17 |
Family
ID=51434099
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410293554.5A Active CN104017056B (en) | 2014-06-27 | 2014-06-27 | ST2 protein inhibitor polypeptide and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104017056B (en) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2001218871A1 (en) * | 2000-03-21 | 2001-10-03 | Takao Arai | Monoclonal antibody and method and kit for the immunoassay of soluble human st2 with the use of the same |
| PL2734222T3 (en) * | 2011-07-18 | 2017-03-31 | Critical Care Diagnostics, Inc. | Methods of treating cardiovascular diseases and predicting the efficacy of exercise therapy |
-
2014
- 2014-06-27 CN CN201410293554.5A patent/CN104017056B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN104017056A (en) | 2014-09-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ma et al. | Topical application of temperature-sensitive caerin 1.1 and 1.9 gel inhibits TC-1 tumor growth in mice | |
| CN104017056B (en) | ST2 protein inhibitor polypeptide and application thereof | |
| CN104059130B (en) | about ST2 protein inhibitor polypeptide and application thereof | |
| CN104017055B (en) | A kind of about ST2 protein inhibitor polypeptide and application thereof | |
| CN104666320A (en) | Application of 3,5,3',4'-trihydroxy-stilbene-3'-b-D-glucoside in preparation of medicines for treating cancers | |
| CN103385872B (en) | Pharmaceutical composition of a kind of Hepatoma therapy and preparation method thereof | |
| CN104017057B (en) | A kind of ST2 protein inhibitor polypeptide and application thereof | |
| CN104045689B (en) | A kind of about somatostatin receptor agonist polypeptide and application thereof | |
| CN103479642B (en) | Nano sodium cantharidinate composition and preparation method thereof | |
| CN103393639A (en) | Medicinal composition for treating lung cancer and preparation method thereof | |
| CN103948614B (en) | The pharmaceutical applications of otoginsenoside and salt thereof | |
| CN105517558A (en) | Filipendula vulgaris extract and uses thereof | |
| CN103739669A (en) | Polypeptide capable of inhibiting interleukin-6 and application thereof | |
| CN103169693A (en) | Application of wogonin derivant in preparation of drug for treating liver cancer | |
| CN101966192A (en) | Application of orsythoside A in preparation of medicament for treating herpes simplex | |
| CN104017053B (en) | A kind of PER2 protein agonist polypeptide and application thereof | |
| CN104004060B (en) | Cyclin D protein inhibitor polypeptide and application thereof | |
| CN105198965A (en) | VEGFR2 blocker polypeptide and application thereof | |
| Ma et al. | Effect of Allicin on Tumor Tissue and Its Mechanism in Mice with Tumor-bearing Endometrial Carcinoma. | |
| CN103222972A (en) | Application of traditional Chinese medicine extraction component Jaceosidin | |
| Fayed et al. | Local BCG injection administered to patients with flat condyloma of the cervix | |
| Yoon et al. | UP-3.007: Histone Deacetylase Inhibitor Trichostatin A Induces Apoptosis in Human Invasive Bladder Cancer through the Caspase Dependent Pathway | |
| CN104694520A (en) | Hydrolyzed profibrinolysin polypeptide and application thereof | |
| CN104031122B (en) | Relevant Cyclin D protein inhibitor polypeptide and application thereof | |
| Ozawa et al. | UP-3.008: Inhibition of Bladder Tumor Growth by Histone Deacetylase Inhibitor |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| 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 |
|
| 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. |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |