CN104017053B - A kind of PER2 protein agonist polypeptide and application thereof - Google Patents
A kind of PER2 protein agonist polypeptide and application thereof Download PDFInfo
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- CN104017053B CN104017053B CN201410288283.4A CN201410288283A CN104017053B CN 104017053 B CN104017053 B CN 104017053B CN 201410288283 A CN201410288283 A CN 201410288283A CN 104017053 B CN104017053 B CN 104017053B
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- polypeptide
- per2
- protein agonist
- agonist polypeptide
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- 102100035787 Period circadian protein homolog 2 Human genes 0.000 title claims abstract description 28
- 229940076376 protein agonist Drugs 0.000 title claims description 18
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims abstract description 27
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims abstract description 11
- 201000004101 esophageal cancer Diseases 0.000 claims abstract description 11
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Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention relates to drug world, be specifically related to that there is promotion PER2 protein expression, the polypeptide for the treatment of treatment esophageal carcinoma.Its sequence be TQTDPLYIGGSALF be brand-new sequence, this polypeptide can vitro inhibition esophageal cancer cell TE1 and Eca109 cell proliferation, treat esophageal carcinoma；In body lotus tumor model experiment, successfully add the survival rate of mice, there is potential new drug development value.
Description
Technical field
The present invention relates to PER2 protein agonist polypeptide 1 and application thereof, be specifically related to have promotion PER2 protein expression, control
Treat the polypeptide of esophageal carcinoma.
Background technology
Operation, radiotherapy, chemotherapy, biology can be selected according to diverse location, the staging of focus in the treatment of the esophageal carcinoma
Targeted therapy mode.Cancerous issue and metastatic lymph node are often excised in the operation of the esophageal carcinoma, and tubulose stomach replaces its function.But operation
It is difficult to excise cancerous tissue and subclinical focus completely.Next is exactly chemicotherapy, but the equal normal tissue of both therapeutic modalities
Organ has obvious side reaction, and further raising curative effect the damage reducing normal tissue are the problems being worth research.The most raw
Thing targeting therapy on tumor is the most promising, and targeted therapy is to lead to for blocking certain or multiple signal in tumor generating process
Road, reaches to treat the purpose of tumor.
Explore tumor etiology, during finding the Therapeutic Method of tumor, find disorder and the tumor of biorhythm
Development is occurred to have much relations.The disorder of biorhythm has certain relation with the generation development of the esophageal carcinoma.Raw with modern time
The thing section of learning to do detects the change of tumor rhythm gene has become the emerging research topic of esophageal carcinoma therapy.
The PER2 albumen that Ciradian gene PER2 expresses all becomes Spontaneously beating rhythm to become with under normal brightness cycling condition
Change.PER2 is the closest with relation between tumor in PER serial genes.Research shows, PER2 albumen is low table in human esophageal carcinoma
Reach, and high expressed in cancer beside organism, PER2 can regard a protective gene as, and its expression can raise antioncogene
P53, lowers the expression of oncogene c-cmyc.The expression of PER2 can suppress the propagation of oncocyte, make the funeral of immortalization capacity
Lose, simultaneously can be by blocking the G2/M phase of oncocyte, reaching cell cycle regulation increases the purpose of radiation sensitivity.
The reduction of PER2 protein function is the key factor that the esophageal carcinoma occurs.Therefore, PER2 protein expression, suppression are promoted
The esophageal carcinoma develops, and is the novel targets of the treatment esophageal carcinoma.But, not yet have the treatment of the PER2 protein agonist polypeptide of exploitation maturation
The medicine of the esophageal carcinoma.
PER2 protein agonist polypeptide in this patent is proved in the esophageal 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 PER2 protein agonist, has good curative effect to the esophageal carcinoma.
Technical scheme
PER2 protein agonist polypeptide, it is characterised in that its sequence is TQTDPLYIGGSALF.
The application in preparation treatment esophageal carcinoma medicine of the PER2 protein agonist polypeptide.
Beneficial effect
Utilizing solid-phase synthesis chemosynthesis PER2 protein agonist polypeptide, this polypeptide has brand-new sequence, this polypeptide
Can vitro inhibition esophageal cancer cell TE1 and Eca109 cell proliferation, treat esophageal carcinoma；Body lotus tumor model experiment successfully increases
Add the survival rate of mice, there is potential new drug development value.
Detailed description of the invention
The polypeptide that the present invention relates to is by gill biochemical (Shanghai) synthesis.
Embodiment 1
The effect that people esophageal cancer cell TE1 is bred by PER2 protein agonist polypeptide.
Use MTT colorimetry.By the TE1 cell of logarithmic growth, add in 96 well culture plates with 1.0 × 105, cultivate
24h, experimental port, positive drug control hole are separately added into the Experimental agents PER2 protein agonist polypeptide of variable concentrations and the positive is right
According to agent vincristine；Blank group adds the solvent of same volume.Every hole sets five multiple holes, cultivates 48h, respectively 0h, 2h,
The every hole of 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%.The IC50 calculating Experimental agents is 6.40 μMs.When concentration is 6.40 μMs, to Eca109 proliferation inhibition rate
It is 70.3%.
Embodiment 2
The effect that people esophageal cancer cell ECA109 is bred by PER2 protein agonist polypeptide.
Use MTT colorimetry.By the ECA109 cell of logarithmic growth, add in 96 well culture plates with 1.0 × 105,
Cultivate 24h, experimental port, positive drug control hole be separately added into variable concentrations Experimental agents PER2 protein agonist polypeptide and
Positive control medicine vincristine；Blank group adds the solvent of same volume.Every hole sets five multiple holes, cultivates 48h, exists respectively
The every hole of 0h, 2h, 8h, 14h, 20h, 24h, 36h, 48h adds MTT, after effect 4h, adds DMSO, hatches 30min, at enzyme mark
Absorbance A value is measured, by formula growth of tumour cell suppression ratio=(1-experimental group light absorption value/matched group is inhaled at instrument 620nm
Light value) × 100%.The IC50 calculating Experimental agents is 7.13 μMs.When concentration is 7.13 μMs, to Eca109 Proliferation Ability
Rate is 66.4%.
Embodiment 3
Internal vigor with tumor model detection PER2 protein agonist polypeptide.
Set up Eca109 tumor model, positive control medicine vincristine；Blank group adds the solvent of same volume, experiment
Group sets 3 dosage: 6,12,24 mg/Kg.After 21 days, observe mouse survival quantity, calculate survival rate.Result shows, PER2 egg
White agonist polypeptide can protect white mice effectively, improves the survival rate of tumor-bearing mice, and survival rate reaches 78.4%.
Embodiment 4
The inhibition test that people's esophageal cancer cell TE1 nude mouse xenograft tumor is grown by polypeptide
Take the logarithm people's esophageal cancer cell TE1 cell strain of trophophase, be aseptically prepared as 5 × 107/ml cell and hang
Liquid, is inoculated in axillary fossa 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 extremely
By animal random packet after 100-200mm3.Use the method measuring tumor footpath, dynamically observe the antitumous effect of tested polypeptide.Swollen
The pendulous frequency of tumor diameter 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；Polypeptide senior middle school
Low group, respectively with 20mg/kg, 10mg/kg, 5mg/kg, is administered once daily.After off-test, sacrifice, operation strips tumor mass
Weigh.
The inhibitory action that people's esophageal cancer cell TE1 nude mouse xenograft tumor is grown by table 1 polypeptide
Therefore, people's esophageal cancer cell TE1 transplanted tumor in nude mice growth inhibition test result is shown, with negative control group by polypeptide
Comparing, polypeptide 20mg/kg group has the inhibitory action of pole significance, polypeptide 10mg/ to the growth of people's esophageal cancer cell TE1 transplanted tumor
Kg group has the inhibitory action of significance to the growth of people's esophageal cancer cell TE1 transplanted tumor.Compared with positive controls paclitaxel, many
The body weight of laboratory animal is had not significant impact by peptide, has no obvious toxicity.
SEQUENCE LISTING
<110>Suzhou Pu Luoda bio tech ltd
<120>a kind of PER2 protein agonist polypeptide and application thereof
<130>
<160> 1
<170> PatentIn version 3.3
<210> 1
<211> 14
<212> PRT
<213>artificial sequence
<400> 1
Thr Gln Thr Asp Pro Leu Tyr Ile Gly Gly Ser Ala Leu Phe
1 5 10
Claims (5)
1.PER2 protein agonist polypeptide, it is characterised in that its sequence is TQTDPLYIGGSALF.
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. PER2 protein agonist polypeptide as claimed in claim 1, it is characterised in that effective dose is 10mg/kg.
5. the PER2 protein agonist polypeptide as claimed in claim 1 application in preparation treatment esophageal cancer medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410288283.4A CN104017053B (en) | 2014-06-25 | 2014-06-25 | A kind of PER2 protein agonist polypeptide and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410288283.4A CN104017053B (en) | 2014-06-25 | 2014-06-25 | A kind of PER2 protein agonist polypeptide and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104017053A CN104017053A (en) | 2014-09-03 |
| CN104017053B true CN104017053B (en) | 2016-09-28 |
Family
ID=51434096
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410288283.4A Active CN104017053B (en) | 2014-06-25 | 2014-06-25 | A kind of PER2 protein agonist polypeptide and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104017053B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000020585A1 (en) * | 1998-10-02 | 2000-04-13 | The Rockefeller University | Mammalian timeless and methods of use thereof |
| JP2006008583A (en) * | 2004-06-25 | 2006-01-12 | Sony Corp | 15d-pgj2 and method using 15d-pgj2 |
-
2014
- 2014-06-25 CN CN201410288283.4A patent/CN104017053B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000020585A1 (en) * | 1998-10-02 | 2000-04-13 | The Rockefeller University | Mammalian timeless and methods of use thereof |
| JP2006008583A (en) * | 2004-06-25 | 2006-01-12 | Sony Corp | 15d-pgj2 and method using 15d-pgj2 |
Non-Patent Citations (2)
| Title |
|---|
| PER2在食管癌及癌旁组织中的差异性表达及意义;李婷婷等;《四川生理科学杂志》;20120319;第33卷(第4期);摘要部分，第154页左栏第2段 * |
| 人食管癌细胞特异性结合肽的噬菌体肽库筛选及鉴定;单雪;《中国优秀硕士学位论文全文数据库》;20121015;全文 * |
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| Publication number | Publication date |
|---|---|
| CN104017053A (en) | 2014-09-03 |
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