CN104031122A - Related Cyclin D protein inhibitor polypeptide and application thereof - Google Patents
Related Cyclin D protein inhibitor polypeptide and application thereof Download PDFInfo
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- CN104031122A CN104031122A CN201410282013.2A CN201410282013A CN104031122A CN 104031122 A CN104031122 A CN 104031122A CN 201410282013 A CN201410282013 A CN 201410282013A CN 104031122 A CN104031122 A CN 104031122A
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- cyclin
- polypeptide
- cell
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- inhibitor polypeptide
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Abstract
The invention relates to the field of medicines, particularly a polypeptide capable of inhibiting expression of Cyclin D protein and treating amphicyte lymphoma. The sequence is SVSYFKCVQKEVLPSMRKIV which is a brand-new sequence. The polypeptide can be used for inhibiting cell proliferation and migration of amphicyte lymphoma cells G519 and z138 and treating amphicyte lymphoma, and has potential new medicine development value.
Description
Technical field
The present invention relates to Cyclin D protein inhibitor polypeptide 3 and application thereof, be specifically related to have and suppress Cyclin D protein expression, treat the polypeptide of lymphoma mantle cell.
Background technology
Lymphoma mantle cell (MCL) is a kind of with t(11; 14) (q13; Q32) and the cyclin D1 overexpression B Cell Non-Hodgkin's that is feature, belong to the pernicious lymphoma of moderate, long-term survival rate is very low.Be common in the elderly, in the majority with the male sex, the median age 60 years old.MCL easily recurs, and is the lymphoma hypotype that long term survival rate is minimum, and median survival interval is 3～5 years.Clinical manifestation is aggressive, and disease progression is very fast, has extensive lymph node involvement more, tie outer pathology common, liver, spleen, peripheral blood and marrow have infiltration more, and often accompany multiple gi tract to involve with neural system and infiltrate, when 80%～90% patient makes a definite diagnosis, be Ann Arbor III～IV phase.Treat at present and take chemotherapy or merge stem cell transplantation as main, although improved to some extent MCL patient's CR, lead, but still can not improve patient's long-term survival rate.At present biological targeting treatment tumour is very promising, and targeted therapy is for blocking certain or a plurality of signal path in tumour generating process, reaches the object for the treatment of tumour.
Cyclin albumen is being controlled the cycle of rest, growth and the division of cell as " check point " guarder.Wherein, Cyclin D is the important target spot of growth cycle of controlling cell.Cyclin D has determined when cell starts to generate DNA, for division forms new cell, prepares.Cyclin D overexpression in being permitted eurypalynous cancer, the too fast growth of irritation cell forms tumour.Research discovery, blocking-up cyclin D1 albumen can order about breast cancer cell and enter aging state, irreversibly stops their growth cycle.In T-ALL leukemia mouse, suppress Cyclin D and can cause cancer cells self-destruction (a programmed death process that is called apoptosis).Therefore, suppressing Cyclin D protein expression, suppress lymphoma mantle cell development, is the novel targets for the treatment of lymphoma mantle cell.But, not yet have the medicine of the treatment lymphoma mantle cell of the ripe Cyclin D protein inhibitor polypeptide of exploitation
Cyclin D protein inhibitor polypeptide 3 in this patent has proved in lymphoma mantle cell 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 Cyclin D protein expression, and treatment lymphoma mantle cell is had to good curative effect.
technical scheme
Cyclin D protein inhibitor polypeptide, is characterized in that its sequence is SVSYFKCVQKEVLPSMRKIV.
A pharmaceutical composition, is characterized in that it comprises as claimed in claim 1 polypeptide and more than one are pharmaceutically acceptable
Vehicle, weighting agent, tackiness agent, lubricant, disintegrating agent or stablizer.
Described pharmaceutical composition, is characterized in that, described composition is injection.
Described Cyclin D protein inhibitor polypeptide, is characterized in that effective dose is 10mg/kg.
The application of Cyclin D protein inhibitor polypeptide 3 in treatment lymphoma mantle cell medicine.
beneficial effect
Cyclin D protein inhibitor polypeptide 3, this polypeptide has brand-new sequence, and this polypeptide can vitro inhibition lymphoma mantle cell cell G519 and z138 cell proliferation and migration, and treatment lymphoma mantle cell has potential new drug development and is worth.
Embodiment
the polypeptide the present invention relates to is synthetic by gill biochemical (Shanghai).
Embodiment 1
The effect of Cyclin D protein inhibitor polypeptide to people's lymphoma mantle cell cell z138 propagation.
Adopt MTT colorimetry.By the z138 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 Cyclin D protein inhibitor polypeptide 3 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, in 0h, 2h, 8h, 14h, 20h, 24h, the every hole of 36h, 48h, add MTT respectively, after effect 4h, add DMSO, hatch 30min, at microplate reader 620nm place, measure absorbance A value, by formula growth of tumour cell inhibiting rate=(1-experimental group light absorption value/control group light absorption value) * 100%.To the maximum proliferation inhibition rate of z138, be 92.75%.
Table 1. polypeptide is to the effect of z1383 cell inhibitory effect
Embodiment 2
The effect of Cyclin D protein inhibitor polypeptide 3 people's lymphoma mantle cell cell G519 propagation.
Adopt MTT colorimetry.By the G519 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 Cyclin D protein inhibitor polypeptide 3 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, in 0h, 2h, 8h, 14h, 20h, 24h, the every hole of 36h, 48h, add MTT respectively, after effect 4h, add DMSO, hatch 30min, at microplate reader 620nm place, measure absorbance A value, by formula growth of tumour cell inhibiting rate=(1-experimental group light absorption value/control group light absorption value) * 100%.To the maximum proliferation inhibition rate of Mino, be 64.71%.
Embodiment 3
The inhibition test of 1 pair of people's lymphoma mantle cell cell G519 bare mouse different species Growth of Tumors Transplanted of Cyclin D protein inhibitor polypeptide
People's lymphoma mantle cell cell G519 cell 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, administration is 1 time weekly; 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 2 polypeptide to people's lymphoma mantle cell cell G519 bare mouse different species Growth of Tumors Transplanted
Result: polypeptide shows people's lymphoma mantle cell cell G519 transplanted tumor in nude mice growth inhibition test result, compare with negative control group, polypeptide 20mg/kg, 10mg/kg and 5mg/kg group all have the restraining effect of utmost point significance to the growth of people's lymphoma mantle cell cell G519 transplanted tumor.Compare with positive controls taxol, polypeptide does not have a significant effect to the body weight of laboratory animal, has no obvious toxic side effects, and taxol toxicity is larger, and the weight of animals declines, and in experimentation, animal has death.
SEQUENCE LISTING
Pu Luoda bio tech ltd, <110> Suzhou
The relevant Cyclin D of <120> protein inhibitor polypeptide and application thereof
<130>
<160> 1
<170> PatentIn version 3.3
<210> 1
<211> 20
<212> PRT
<213> artificial sequence
<400> 1
Ser Val Ser Tyr Phe Lys Cys Val Gln Lys Glu Val Leu Pro Ser Met
1 5 10 15
Arg Lys Ile Val
20
Claims (5)
1.Cyclin D protein inhibitor polypeptide, is characterized in that its sequence is QAQQNMDPKAAEEEEEE.
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. Cyclin D protein inhibitor polypeptide as claimed in claim 1, is characterized in that effective dose is 10mg/kg.
The application of 5.Cyclin D protein inhibitor polypeptide in treatment lymphoma mantle cell medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410282013.2A CN104031122B (en) | 2014-06-23 | 2014-06-23 | Relevant Cyclin D protein inhibitor polypeptide and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410282013.2A CN104031122B (en) | 2014-06-23 | 2014-06-23 | Relevant Cyclin D protein inhibitor polypeptide and application thereof |
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| Publication Number | Publication Date |
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| CN104031122A true CN104031122A (en) | 2014-09-10 |
| CN104031122B CN104031122B (en) | 2016-05-11 |
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| CN201410282013.2A Expired - Fee Related CN104031122B (en) | 2014-06-23 | 2014-06-23 | Relevant Cyclin D protein inhibitor polypeptide and application thereof |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1901906A (en) * | 2003-11-04 | 2007-01-24 | 梅奥医学教育和研究基金会 | Cci-779 for treating mantle cell lymphoma |
| CN101583359A (en) * | 2006-08-03 | 2009-11-18 | 细胞基因公司 | Use of 3- (4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione for the treatment of mantle cell lymphomas |
-
2014
- 2014-06-23 CN CN201410282013.2A patent/CN104031122B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1901906A (en) * | 2003-11-04 | 2007-01-24 | 梅奥医学教育和研究基金会 | Cci-779 for treating mantle cell lymphoma |
| CN101583359A (en) * | 2006-08-03 | 2009-11-18 | 细胞基因公司 | Use of 3- (4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione for the treatment of mantle cell lymphomas |
Non-Patent Citations (1)
| Title |
|---|
| PEREZ-GALAN P.等: "The proteasome inhibitor bortezomib induces apoptosis in mantle-cell lymphoma through generation of ROS and Noxa activation independent of p53 status", 《BLOOD》, vol. 107, no. 1, 1 January 2006 (2006-01-01), pages 257 - 264 * |
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| Publication number | Publication date |
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| CN104031122B (en) | 2016-05-11 |
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| C41 | Transfer of patent application or patent right or utility model | ||
| CB03 | Change of inventor or designer information |
Inventor after: Luo Judong Inventor after: Zhou Xifa Inventor after: Lu Zhonghua Inventor after: Tang Yiting Inventor after: Tang Hua Inventor after: Lu Xujing Inventor before: Luo Ruixue |
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Effective date of registration: 20160414 Address after: 213000 Jiangsu city of Changzhou province Huaide Road No. 1 Applicant after: Changzhou Cancer Hospital 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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Granted publication date: 20160511 Termination date: 20170623 |