CN104045692B - A kind of Npas2 protein agonist polypeptide and application thereof - Google Patents
A kind of Npas2 protein agonist polypeptide and application thereof Download PDFInfo
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- CN104045692B CN104045692B CN201410288077.3A CN201410288077A CN104045692B CN 104045692 B CN104045692 B CN 104045692B CN 201410288077 A CN201410288077 A CN 201410288077A CN 104045692 B CN104045692 B CN 104045692B
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- polypeptide
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- protein agonist
- agonist polypeptide
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Abstract
The present invention relates to pharmaceutical field, it is specifically related to that there is promotion Npas2 protein expression, the polypeptide for the treatment of treatment mammary cancer. Its sequence is LQTHYAYITYHQ is brand-new sequence, and this polypeptide can promote Npas2 protein expression in body, treatment mammary cancer. Improve tumor-bearing mice survival rate in body; Suppress the propagation of human breast cancer cell line Bcap-37, migration; There is potential new drug development value.
Description
Technical field
The present invention relates to Npas2 protein agonist polypeptide 1 and application thereof, it is specifically related to that there is promotion Npas2 protein expression, the polypeptide for the treatment of mammary cancer.
Background technology
Diel rhythm is the multiple biological phenomenas such as the physiological function of organism, biochemical indicator and physiological behavior is a kind of biorhythm of rhythmicity vibration taking 24 hours as the cycle. Physiological clock system relates to all respects of the physiology of body system, biochemistry and behavior, peripheral organs, tissue and cell is affected at integral level, cell levels, control and adjustment metabolism, sleep and awakening, internal secretion, immunity and cell cycle etc., make vital movement harmonious; On a molecular scale, regulation and control and cell cycle, cell proliferation and withering are died, relevant a series of cytokines are replied in DNA damage reparation, in close relations with the generation of malignant tumour, development and treatment etc. Therefore circadian rhythm disorder can cause clock gene and the unconventionality expression of associated protein product thereof, thus impels tumour to occur, and accelerates tumour progression.
Mammary cancer is one of common malignant tumour of women, and the lift velocity of its mortality ratio ranks first place at female malignant. The research of epidemiology shows, the destruction of diel rhythm and the generation of mammary cancer are closely related. Npas2 expresses obviously downward in mammary cancer, in close relations with the generation of mammary cancer, pathology and clinical stages. Npas2 gene is maximum clock gene in Mammals, it it is the homologous gene of Clock, can by regulating and controlling and disturb oncogene, cancer suppressor gene and cell cycle, cell proliferation and apoptosis-related genes, many-sided generation and the development that may take part in mammary cancer of the process etc. at cell cycle regulating, DNA damage reparation response and Tumor growth inhibition. Research shows, the low expression of Npas2 albumen and tumour tumorous size, invasive depth are relevant, and breast cancer development is had protective effect by Npas2 albumen high expression level. In mammary cancer precancerous lesion, Npas2 expresses and strengthens, it is possible to stop precancerous lesion to cancerate.It is the important factor that mammary cancer occurs that Npas2 protein function reduces. Therefore, promote Npas2 protein expression, suppress breast cancer development, be the novel targets for the treatment of mammary cancer. But, the medicine of the treatment mammary cancer of the Npas2 protein agonist polypeptide not yet having exploitation ripe
Npas2 protein agonist polypeptide 1 in this patent has proved in mammary cancer effective, has the prospect of exploitation in other tumor models.
Summary of the invention
Goal of the invention
The present invention provides brand-new sequence, and this sequence Npas2 protein agonist polypeptide, has good curative effect to mammary cancer.
Technical scheme
Npas2 protein agonist polypeptide, it is characterised in that its sequence is LQTHYAYITYHQ.
A kind of pharmaceutical composition, it is characterised 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, it is characterised in that, described composition is injection.
Described Npas2 protein agonist polypeptide, it is characterised in that effective dose is 10mg/kg.
The application of described Npas2 protein agonist polypeptide in preparation treatment breast cancer medicines.
Useful effect
Utilizing solid-phase synthesis chemosynthesis Npas2 protein agonist polypeptide, this polypeptide has brand-new sequence, and this polypeptide can promote Npas2 protein expression in body, treatment mammary cancer. Improve tumor-bearing mice survival rate in body; Suppress the propagation of human breast cancer cell line Bcap-37, migration; There is potential new drug development value.
Embodiment
The present invention relates to polypeptide to synthesize by Ji Er biochemistry (Shanghai).
Embodiment 1
The effect that human breast cancer cell line Bcap-37 is bred by Npas2 protein agonist polypeptide.
Adopt MTT colorimetry. By MIAPACA II cell of logarithmic growth, adding in 96 well culture plates with 1.0 �� 105, cultivate 24h, experimental port, positive drug control hole add Experimental agents Npas2 protein agonist 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, cultivate 48h, and 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 7.52 ��Ms.
Embodiment 2
Npas2 protein agonist polypeptide is to the inhibition test of human breast cancer cell line Bcap-37 bare mouse different species Growth of Tumors Transplanted
The human breast cancer cell line Bcap-37 cell strain taken the logarithm vegetative period, is aseptically prepared into 5 �� 107/ ml cell suspension, is inoculated in armpit on the right side of naked mouse with 0.1ml subcutaneous. 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 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 equivalent physiological saline, every day 1 time; Taxol group 10mg/kg, Per-Hop behavior 1 time; RhEndostatin group 2.5mg/kg, administration every day 1 time; High, normal, basic group of polypeptide respectively with 20mg/kg, 10mg/kg, 5mg/kg, administration every day 1 time. After test terminates, sacrifice, operation strips knurl block and weighs.
Table 1 polypeptide is to the restraining effect of human breast cancer cell line Bcap-37 bare mouse different species Growth of Tumors Transplanted
Human breast cancer cell line Bcap-37 transplanted tumor in nude mice growth-inhibiting test-results is shown by polypeptide, and compared with negative control group, the growth of human breast cancer cell line Bcap-37 transplanted tumor is all had the restraining effect of pole significance by polypeptide 20mg/kg, 10mg/kg and 5mg/kg group.Compared with positive controls taxol, the body weight of laboratory animal is not had a significant effect by polypeptide, has no obvious toxic side effects, and survival rate improves.
SEQUENCELISTING
<110>Suzhou Pu Luoda bio tech ltd
<120>a kind of Npas2 protein agonist polypeptide and application thereof
<130>
<160>1
<170>PatentInversion3.3
<210>1
<211>12
<212>PRT
<213>artificial sequence
<400>1
LeuGlnThrHisTyrAlaTyrIleThrTyrHisGln
1510
Claims (5)
1.Npas2 protein agonist polypeptide, it is characterised in that its sequence is LQTHYAYITYHQ.
2. a pharmaceutical composition, it is characterised in that it comprises polypeptide and more than one pharmaceutically acceptable weighting agents, tackiness agent, lubricant, disintegrating agent or stablizer as claimed in claim 1.
3. pharmaceutical composition as claimed in claim 2, it is characterised in that, described composition is injection.
4. Npas2 protein agonist polypeptide as claimed in claim 1, it is characterised in that effective dose is 10mg/kg.
5. Npas2 protein agonist polypeptide as claimed in claim 1 treats the application in breast cancer medicines in preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410288077.3A CN104045692B (en) | 2014-06-25 | 2014-06-25 | A kind of Npas2 protein agonist polypeptide and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410288077.3A CN104045692B (en) | 2014-06-25 | 2014-06-25 | A kind of Npas2 protein agonist polypeptide and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104045692A CN104045692A (en) | 2014-09-17 |
| CN104045692B true CN104045692B (en) | 2016-06-08 |
Family
ID=51499130
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410288077.3A Active CN104045692B (en) | 2014-06-25 | 2014-06-25 | A kind of Npas2 protein agonist polypeptide and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104045692B (en) |
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2014
- 2014-06-25 CN CN201410288077.3A patent/CN104045692B/en active Active
Non-Patent Citations (3)
| Title |
|---|
| Genbank:EAX01830.1;Venter,J.C.等;《Genbank》;20140514;全文 * |
| The Circadian Gene NPAS2, a Putative Tumor Suppressor, Is Involved in DNA Damage Response;Aaron E. Hoffman等;《Mol Cancer Res》;20080930;第6卷(第9期);摘要 * |
| 生物钟基因Npas2在老年乳腺癌患者中的表达及其临床意义;李新白等;《中国老年学杂志》;20120531;第32卷(第9期);全文 * |
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| Publication number | Publication date |
|---|---|
| CN104045692A (en) | 2014-09-17 |
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| 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: Chen Wei Inventor after: Ruan Hongqiang Inventor after: Li Mingzhu Inventor after: Dai Jie Inventor before: Luo Ruixue |
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| COR | Change of bibliographic data | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20160509 Address after: 200030 No. 2, building 500, Caobao Road, Shanghai, Xuhui District Applicant after: Shanghai Applied Protein Technology 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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| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |