CN104045689B - A kind of about somatostatin receptor agonist polypeptide and application thereof - Google Patents
A kind of about somatostatin receptor agonist polypeptide and application thereof Download PDFInfo
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- CN104045689B CN104045689B CN201410286694.XA CN201410286694A CN104045689B CN 104045689 B CN104045689 B CN 104045689B CN 201410286694 A CN201410286694 A CN 201410286694A CN 104045689 B CN104045689 B CN 104045689B
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- polypeptide
- receptor agonist
- somatostatin
- somatostatin receptor
- tumor
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Abstract
The present invention relates to drug world, be specifically related to that there is Developing restraint chalone and express, the polypeptide for the treatment of hepatocarcinoma.A kind of about somatostatin receptor agonist polypeptide and application thereof, its sequence be WDDLPFFTVNIVNLAVA be brand-new sequence, external promotion somatostatin combine, suppression human liver cancer cell HepG2 propagation, and in testing in vivo, improve tumor-bearing mice survival rate, there is potential new drug development value.
Description
Technical field
The present invention relates to somatostatin receptor agonist polypeptide 4 and application thereof, be specifically related to that there is promotion growth and press down
Element receptor active, the polypeptide for the treatment of hepatocarcinoma.
Background technology
Hepatocarcinoma is one of modal malignant tumor of China, since the nineties in 20th century, and China's mortality of liver cancer
Have been raised to the 2nd of malignant tumor, there are about 130,000 people every year and die from hepatocarcinoma.Primary hepatocarcinoma PD is fast,
If without treatment, Natural Survival phase average out to 4.3 months, even if excision prognosis is the most undesirable, life in 5 years
The rate of depositing is 37.2%, and 5 years survival rates of small liver cancer Post operation are also only 53.5%.Affect liver cancer patient operative treatment effect
The main cause of fruit is recurrence and transfer.Recurrence of PHC rate may be up to more than 60%, though small liver cancer art
Rear relapse rate is also up to 40%.At present Biological target therapy tumor is the most promising, targeted therapy be for
Tumor generating process blocks certain or multiple signal path, reaches to treat the purpose of tumor.
Somatostatin, in addition to having suppression intestinal hormone secretion, also has suppression digestive tract tumor such as gastric cancer, pancreas
The effect of the tumor cell proliferation such as adenocarcinoma, hepatocarcinoma, thus somatostatin becomes the medicine of potential treatment tumor,
The effects such as especially for hepatocarcinoma, it has suppression tumor growth, inducing cell apoptosis.Have document report at present
Road, is used for the treatment of advanced liver cancer by the long-acting somatostatin anologues of synthetic and obtains certain effect.Medicine
Pharmacological research confirms, somatostatin and somatostatin receptor (SSTR) the specific bond ability in tumor tissues
Play the effect of suppression tumor growth.All there is the expression of SSTR in the many entity tumors including hepatocarcinoma,
And in vitroreceptorautoradiography and radioligand binding are it has also been found that there is SSTR in liver cancer tissue.Therefore,
Somatostatin receptor agonist, can promote the activity of SSTR, the growth of suppression tumor, is prevention and treatment
The novel targets of liver cancer recurrence.But, not yet have the treatment liver of the somatostatin receptor agonist polypeptide of exploitation maturation
The medicine of cancer.
Somatostatin receptor agonist polypeptide in this patent is proved in hepatocarcinoma effectively, to be had in other tumors
The prospect of exploitation in model.
Summary of the invention
Goal of the invention
The present invention provides brand-new sequence, this sequence somatostatin receptor agonist, multiple to prevention and treatment hepatocarcinoma
Send out and there is good curative effect.
Technical scheme
Somatostatin receptor agonist polypeptide, it is characterised in that its sequence is WDDLPFFTVNIVNLAVA.
A kind of pharmaceutical composition, it is characterised in that its comprise polypeptide as claimed in claim 1 and more than one
Pharmaceutically acceptable excipient, filler, binding agent, lubricant, disintegrating agent or stabilizer.
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 preparation treatment liver-cancer medicine of the described somatostatin receptor agonist polypeptide.
Beneficial effect
Utilizing solid-phase synthesis chemosynthesis somatostatin receptor agonist polypeptide, this polypeptide has brand-new sequence,
This polypeptide can promote the activity of somatostatin receptor, prevents and treats liver cancer recurrence.Promote somatostatin in vitro
In conjunction with, suppression human liver cancer cell HepG2 propagation, and in vivo test in improve tumor-bearing mice survival rate,
There is potential new drug development value.
Detailed description of the invention
The present invention relates to polypeptide by gill biochemical (Shanghai) synthesis.
Embodiment 1
The somatostatin receptor agonist polypeptide 4 impact on growth in vitro inhibin receptor Yu somatostatin affinity.
By the HepG2 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 somatostatin receptor agonist polypeptide of variable concentrations
4 and positive control medicine vincristine；Blank group adds the solvent of same volume, adds meanwhile125I labelling
Somatostatin.Every hole sets five multiple holes, cultivates 48h.Wash away supernatant, with γ-liquid scintillation counter meter
Calculating activity, it is judged that somatostatin receptor and the adhesion of somatostatin, activity intensity is the strongest, in conjunction with
The most, otherwise, activity intensity is the most weak, in conjunction with the fewest.Result shows, with somatostatin receptor agonist
Polypeptide 4 concentration increases, and is combined with somatostatin and is gradually increased, illustrates dense with medicine with somatostatin binding ability
Degree increase and constantly subtract and add.
Table 1 polypeptide is on the HepG2 impact on growth in vitro inhibin receptor Yu somatostatin affinity
Embodiment 2
Somatostatin receptor agonist polypeptide is to the growth of cultured tumor cells in vitro and survival IC50.
Use MTT colorimetry.By the HepG2 cell of logarithmic growth, add 96 hole trainings with 1.0 × 105
Supporting in plate, cultivate 24h, experimental port, positive drug control hole are separately added into the Experimental agents growth of variable concentrations
Inhibin receptor agonist polypeptide 4 and positive control medicine vincristine；Blank group adds the solvent of same volume.
Every hole sets five multiple holes, cultivates 48h, respectively 0h, 2h, 8h, 14h, 20h, 24h, 36h, 48h is every
Hole adds MTT, after effect 4h, adds DMSO, hatches 30min, measures at microplate reader 620nm
Absorbance A value, by formula growth of tumour cell suppression ratio=(1-experimental group light absorption value/matched group light absorption value)
× 100%.The maximal percentage inhibition calculating Experimental agents is 80.28%.
Embodiment 3
The inhibition test that HepG2 cell nude mouse xenograft tumor is grown by polypeptide
Take the logarithm the HepG2 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, wait to swell
Tumor grows to animal random packet after 100-200mm3.Use the method measuring tumor footpath, dynamically observe tested
The antitumous effect of polypeptide.The pendulous frequency of diameter of tumor is to survey 1 time for every 2 days.Administering mode all uses tail quiet
Arteries and veins is injected.Negative control group injection normal saline, every day 1 time；Paclitaxel group 10mg/kg, gives weekly
Medicine 1 time；RhEndostatin group 2.5mg/kg, is administered once daily；High, normal, basic group of polypeptide respectively with 20mg/kg, 10mg/kg,
5mg/kg, is administered once daily.After off-test, sacrifice, operation strips tumor mass and weighs.
The inhibitory action that HepG2 cell nude mouse xenograft tumor is grown by table 2 polypeptide
Therefore, HepG2 cell transplanted tumor in nude mice growth inhibition test result is shown, with negative control group phase by polypeptide
Ratio, polypeptide 20mg/kg group has the inhibitory action of pole significance, polypeptide to the growth of HepG2 cell transplantation tumor
10mg/kg group has the inhibitory action of significance to the growth of HepG2 cell transplantation tumor.Purple with positive controls
China fir alcohol is compared, and the body weight of laboratory animal is had not significant impact by polypeptide, has no obvious toxicity.
SEQUENCE LISTING
<110>
Pu Luoda bio tech ltd, Suzhou
<120>
A kind of about somatostatin receptor agonist polypeptide and application thereof
<130>
<160>
1
<170>
PatentIn version 3.3
<210>
1
<211>
17
<212>
PRT
<213>
Artificial sequence
<400>
1
Trp Asp Asp
Leu Pro Phe Phe Thr Val Asn Ile Val Asn Leu Ala Val
1
5
10
15
Ala
Claims (5)
1. somatostatin receptor agonist polypeptide 4, it is characterised in that its sequence is WDDLPFFTVNIVNLAVA.
2. a pharmaceutical composition, it is characterised in that it comprises polypeptide as claimed in claim 1 and more than one pharmaceutically acceptable excipient, filler, binding agent, lubricant, disintegrating agent or stabilizer.
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 somatostatin receptor agonist polypeptide as claimed in claim 1 application in preparation treatment liver-cancer medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410286694.XA CN104045689B (en) | 2014-06-25 | 2014-06-25 | A kind of about somatostatin receptor agonist polypeptide and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410286694.XA CN104045689B (en) | 2014-06-25 | 2014-06-25 | A kind of about somatostatin receptor agonist polypeptide and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104045689A CN104045689A (en) | 2014-09-17 |
| CN104045689B true CN104045689B (en) | 2016-08-24 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410286694.XA Expired - Fee Related CN104045689B (en) | 2014-06-25 | 2014-06-25 | A kind of about somatostatin receptor agonist polypeptide and application thereof |
Country Status (1)
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Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106366165A (en) * | 2016-08-30 | 2017-02-01 | 苏州普罗达生物科技有限公司 | Sigma receptor stimulant polypeptide and application |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102428371A (en) * | 2009-05-07 | 2012-04-25 | Bcn肽类股份有限公司 | Peptide ligands of somatostatin receptors |
| CN103288919A (en) * | 2006-10-16 | 2013-09-11 | 索尔克生物学研究院 | Receptor (SSTR2)-selective somatostatin antagonists |
-
2014
- 2014-06-25 CN CN201410286694.XA patent/CN104045689B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103288919A (en) * | 2006-10-16 | 2013-09-11 | 索尔克生物学研究院 | Receptor (SSTR2)-selective somatostatin antagonists |
| CN102428371A (en) * | 2009-05-07 | 2012-04-25 | Bcn肽类股份有限公司 | Peptide ligands of somatostatin receptors |
Non-Patent Citations (1)
| Title |
|---|
| 生长抑素受体特异性激动剂对人肝癌细胞生长影响的实验研究;杨少奇 等，;《宁夏医科大学学报》;20110228;126-129 * |
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| CN104045689A (en) | 2014-09-17 |
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| C41 | Transfer of patent application or patent right or utility model | ||
| CB03 | Change of inventor or designer information |
Inventor after: Fan Wenyan Inventor after: Fan Wenbo Inventor after: Xu Na Inventor after: He Guoyang Inventor after: Tu Fei Inventor after: Lv Xiuhua Inventor after: Li Yinghong Inventor before: Luo Ruixue |
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Effective date of registration: 20160627 Address after: 453000 Hongqi District, Henan, Xinxiang Applicant after: Xinxiang Medical College 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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