CN104693280A - Signal-transducer-and-activator-of-transcription suppressing polypeptide and application thereof - Google Patents
Signal-transducer-and-activator-of-transcription suppressing polypeptide and application thereof Download PDFInfo
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- CN104693280A CN104693280A CN201510157199.3A CN201510157199A CN104693280A CN 104693280 A CN104693280 A CN 104693280A CN 201510157199 A CN201510157199 A CN 201510157199A CN 104693280 A CN104693280 A CN 104693280A
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- polypeptide
- transcription factor
- intracellular signaling
- activating transcription
- suppress
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Abstract
The invention relates to the field of drugs, in particular to polypeptide for suppressing signal transducers and activators of transcription and preventing and treating recurrence and metastasis of a breast cancer after an operation is carried out. The sequence of the polypeptide is QLKNLYKDEANPSWPPTEQ and is a brand new sequence. By means of the polypeptide, proliferation and migration of breast cancer cells can be suppressed out of a body, the tumor-bearing mice survival rate can be increased in an in-vivo test, and the potential new drug development value is achieved.
Description
Technical field
The present invention relates to intracellular signaling and activating transcription factor and suppress polypeptide and application thereof, be specifically related to have and suppress intracellular signaling and activating transcription factor, the recurrence of prevention and therapy Mammary cancer cancer and the polypeptide of transfer.
Background technology
Female mammary gland is made up of skin, fibrous tissue, corpus mamma and fat, and mammary cancer is the malignant tumour occurring in mammary gland glandular epithelium tissue.In mammary cancer, 99% occurs in women, and the male sex only accounts for 1%.Current mammary cancer has become the able-bodied kinds of tumor of threat women.
Mammary gland is not the vitals maintaining human life activity, and breast cancer in situ is not fatal; But because breast cancer cell loses Normocellular characteristic, connect loose between cell, easily come off.Cancer cells is once come off, and free cancer cells can send out whole body with blood or lymph liquid, forms transfer, threat to life.How eliminating the distant metastasis of certain cancer or prevent recurrence, is indispensable integral part in cancer treatment method, is also the treatment mammary cancer hot issue inquired at present.
Intracellular signaling and activating transcription factor (STAT) are a kind of important nuclear factors.Activate JAK after cytokine and receptors bind, then activate STAT further.Research finds, STAT3 is unconventionality expression and activation in kinds of tumors tissue, and closely related with the propagation of tumour, differentiation, apoptosis, vasculogenesis, infiltration metastasis and immune evasion.The activity form of STAT3 albumen plays an important role in the Infiltration and metastasis process of kinds of tumors.Therefore, suppress intracellular signaling and activating transcription factor, the combination of intracellular signaling and activating transcription factor and VEGFR3 can be suppressed, suppress ripe lymphatic vessel to be formed, thus suppress the transfer of breast cancer cell, can the recurrence of prevention and therapy Mammary cancer cancer and transfer.
At present, the intracellular signaling of ripe exploitation and activating transcription factor is not had to suppress polypeptide to come out, for recurrence and the transfer of prevention and therapy Mammary cancer cancer.
Summary of the invention
goal of the invention
The invention provides brand-new sequence, this sequence is intracellular signaling and activating transcription factor antagonist, has good curative effect to mammary cancer.
technical scheme
intracellular signaling and activating transcription factor suppress polypeptide, it is characterized in that its sequence is QLKNLYKDEANPSWPPTEQ.
Intracellular signaling and activating transcription factor suppress the application of polypeptide in the recurrence and diversion medicaments of prevention and therapy Mammary cancer cancer.
beneficial effect
Utilize solid-phase synthesis chemosynthesis intracellular signaling and activating transcription factor to suppress polypeptide, this polypeptide has brand-new sequence, and this polypeptide can vitro inhibition intracellular signaling and activating transcription factor, the recurrence of prevention and therapy Mammary cancer cancer and transfer.The intracellular signaling that we find and activating transcription factor suppress polypeptide can suppress Cells Proliferation of Human Breast Cancer vigor simultaneously, and improve tumor-bearing mice survival rate in testing in vivo, have potential new drug development value.
Embodiment
Embodiment 1
Intracellular signaling and activating transcription factor suppress the effect of polypeptide breast cancer cell MCF-7 migration.
Adopt scratch experiment.First use marker pen at 24 orifice plates behind, compare with ruler, evenly must draw horizontal line, approximately every 0.5 ~ 1cm together, cross via hole.Every hole is through 3 lines; By becoming the MCF-7 cell of logarithmic growth, with 1.0 × 10
5add in 24 well culture plates, cultivate 24h.Within second day, compare ruler with 10 μ l rifle heads, perpendicular to horizontal line cut behind, with the point of crossing of cut and horizontal line behind for Orientation observation site; Experimental port, positive drug control hole add the Experimental agents intracellular signaling of different concns respectively and activating transcription factor suppresses polypeptide (the raw work synthesis in Shanghai) and positive control medicine vincristine(VCR); Blank group adds the solvent of same volume, and five multiple holes are established in every hole; Put into 37 DEG C, 5%CO
2incubator, cultivates.By 0,6,12,24,36 hours, take pictures; Measure 0,6,12,24,36h scratch width.With different time points, record the change of three fixed positions place, every hole scratch width, be cell migration distance.According to formulae discovery mobility (migration rate, MR): mobility (MR)=(testing scratch width-experiment scratch width of the 0th hour of n-th hour) × 100%/experiment scratch width of the 0th hour.As a result, suppress peptide concentration to increase with intracellular signaling and activating transcription factor, inhibition of metastasis rate declines gradually, and illustrate that intracellular signaling and activating transcription factor suppress polypeptide that breast cancer cell MCF-7 can be suppressed to move, inhibiting rate is 66.3%.
Embodiment 2
Intracellular signaling and activating transcription factor suppress polypeptide to the growth of vitro culture human breast cancer cell and survival IC50.
Adopt MTT colorimetry.By the human breast cancer cell of logarithmic growth, with 1.0 × 10
5add in 96 well culture plates, cultivate 24h, experimental port, positive drug control hole add the Experimental agents intracellular signaling of different concns respectively and activating transcription factor suppresses polypeptide (the raw work synthesis in Shanghai) and positive control medicine taxol; Blank group adds the solvent of same volume.Five multiple holes are established in every hole, cultivate 48h, respectively 0h, 2h, 8h, 14h, 20h, 24h, 36h, the every hole of 48h adds MTT, after effect 4h, add DMSO, hatch 30min, absorbance A value is measured, by formula human breast cancer cell growth inhibition ratio=(1-experimental group light absorption value/control group light absorption value) × 100% at microplate reader 620nm place.The IC50 calculating Experimental agents is 108.76 μMs.
Embodiment 3
With tumor model detection signal conduction and activating transcription factor suppress polypeptide body in vigor.
Set up MCF-7 tumor model, positive control medicine taxol; Blank group adds the solvent of same volume, and experimental group polypeptide (the raw work synthesis in Shanghai) establishes 3 dosage: 0.75,1.5,3 μMs of mg/Kg.After 21 days, observe mouse survival quantity, calculate survival rate.Result shows, and intracellular signaling and activating transcription factor suppress polypeptide effectively can protect small white mouse, and improve the survival rate of tumor-bearing mice, survival rate reaches 49.2%.
SEQUENCE LISTING
Pu Luoda bio tech ltd, <110> Suzhou
<120> intracellular signaling and activating transcription factor suppress polypeptide and application thereof
<130>
<160> 1
<170> PatentIn version 3.3
<210> 1
<211> 19
<212> PRT
<213> artificial sequence
<400> 1
Gln Leu Lys Asn Leu Tyr Lys Asp Glu Ala Asn Pro Ser Trp Pro Pro
1 5 10 15
Thr Glu Gln
Claims (2)
1. intracellular signaling and activating transcription factor suppress polypeptide, it is characterized in that its sequence is QLKNLYKDEANPSWPPTEQ.
2. intracellular signaling as claimed in claim 1 and activating transcription factor suppress the application of polypeptide in the recurrence and diversion medicaments of prevention and therapy Mammary cancer cancer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510157199.3A CN104693280A (en) | 2015-04-06 | 2015-04-06 | Signal-transducer-and-activator-of-transcription suppressing polypeptide and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510157199.3A CN104693280A (en) | 2015-04-06 | 2015-04-06 | Signal-transducer-and-activator-of-transcription suppressing polypeptide and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104693280A true CN104693280A (en) | 2015-06-10 |
Family
ID=53340867
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510157199.3A Withdrawn CN104693280A (en) | 2015-04-06 | 2015-04-06 | Signal-transducer-and-activator-of-transcription suppressing polypeptide and application thereof |
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| Country | Link |
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| CN (1) | CN104693280A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105037501A (en) * | 2015-08-20 | 2015-11-11 | 倪勤华 | Signal transduction and activating transcription factor inhibiting polypeptide |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101511179A (en) * | 2005-02-25 | 2009-08-19 | 密执安州立大学董事会 | Small molecule inhibitors of STAT3 and the uses thereof |
| CN101854930A (en) * | 2007-09-10 | 2010-10-06 | 波士顿生物医药公司 | A novel group of STAT3 pathway inhibitors and cancer stem cell pathway inhibitors |
| CN102417479A (en) * | 2011-08-29 | 2012-04-18 | 南京大学 | STAT3 small molecular selective inhibitor and preparation method and application thereof |
-
2015
- 2015-04-06 CN CN201510157199.3A patent/CN104693280A/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101511179A (en) * | 2005-02-25 | 2009-08-19 | 密执安州立大学董事会 | Small molecule inhibitors of STAT3 and the uses thereof |
| CN101854930A (en) * | 2007-09-10 | 2010-10-06 | 波士顿生物医药公司 | A novel group of STAT3 pathway inhibitors and cancer stem cell pathway inhibitors |
| CN102417479A (en) * | 2011-08-29 | 2012-04-18 | 南京大学 | STAT3 small molecular selective inhibitor and preparation method and application thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105037501A (en) * | 2015-08-20 | 2015-11-11 | 倪勤华 | Signal transduction and activating transcription factor inhibiting polypeptide |
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| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20150610 |
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| WW01 | Invention patent application withdrawn after publication |