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Jaggedl agonist polypeptide and application thereof

An agonist and kit technology, which is applied in the field of peptides for the treatment of malignant tumors, can solve the problems such as the lack of mature development of Jaggedl agonist peptides, and achieve the effect of improving the survival rate

Inactive Publication Date: 2015-06-03
SUZHOU PULUODA BIOLOGICAL SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] At present, there is no well-developed Jaggedl agonist polypeptide available for the treatment of malignant tumors

Method used

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  • Jaggedl agonist polypeptide and application thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] IC50 of Jagged1 agonist polypeptide on the growth and survival of human melanoma cells cultured in vitro.

[0029] The MTT colorimetric method was used. The logarithmic growth of human melanoma cells was added to a 96-well culture plate at 1.0×105, and cultured for 24 hours. Different concentrations of the experimental drug Jaggedl agonist polypeptide (Shanghai Sangong Synthetic) and positive drug were added to the experimental wells and positive drug control wells respectively. The control drug paclitaxel; the blank group was added the same volume of solvent. Set up five duplicate wells per well, culture for 48h, add MTT to each well at 0h, 2h, 8h, 14h, 20h, 24h, 36h, and 48h respectively, add DMSO after 4h of action, incubate for 30min, and incubate at 620nm in a microplate reader The absorbance A value was measured, according to the formula human melanoma cell growth inhibition rate=(1-absorbance value of the experimental group / absorbance value of the control group)...

Embodiment 2

[0031] IC50 of Jagged1 agonist polypeptide on the growth and survival of human liver cancer stem cells cultured in vitro.

[0032] The MTT colorimetric method was used. The logarithmic growth of human liver cancer stem cells was added to a 96-well culture plate at 1.0×105, and cultured for 24 hours. Experimental wells and positive drug control wells were respectively added with different concentrations of experimental drug Jaggedl agonist polypeptide (Shanghai Sangong Synthetic) and positive control The drug paclitaxel; the same volume of solvent was added to the blank group. Set up five duplicate wells per well, culture for 48h, add MTT to each well at 0h, 2h, 8h, 14h, 20h, 24h, 36h, and 48h respectively, add DMSO after 4h of action, incubate for 30min, and incubate at 620nm in a microplate reader Measure the absorbance A value, according to the formula human liver cancer stem cell growth inhibition rate=(1-absorbance value of the experimental group / absorbance value of the c...

Embodiment 3

[0034] The in vivo activity of Jagged1 agonist polypeptides was tested by tumor model.

[0035] The melanoma tumor model was established, and the positive control drug paclitaxel was added; the same volume of solvent was added to the blank group, and three doses of polypeptide (Shanghai Sangong Synthetic) were set in the experimental group: 2, 4, and 8 mg / Kg. After 21 days, the number of surviving mice was observed, and the survival rate was calculated. The results show that the Jaggedl agonist polypeptide can effectively protect mice and improve the survival rate of tumor-bearing mice. The survival rates of 5, 10, 20 mg / Kg, and positive groups are 97%, 90.1%, 87% and 56% respectively . It shows that the Jaggedl agonist polypeptide has good safety.

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Abstract

The invention discloses a JaggedI agonist polypeptide and an application thereof, relates to the field of medicine and particularly relates to a polypeptide for promoting the combination of the JaggedI and the Notch and treating the malignant tumor. The sequence is a brand-new sequence of YSCTCPGDDSCPGFVGGGCKGKP. The proliferation of the melanoma cell and the liver cancer stem cell can be in vitro inhibited, the survival rate of the tumor-bearing mice in an in vivo test can be increased and a potential new drug development value can be realized.

Description

technical field [0001] The invention relates to a Jagged1 agonist polypeptide and its application, in particular to a polypeptide capable of promoting the combination of Jagged1 and Notch to treat malignant tumors. Background technique [0002] Cancer stem cells are cells in tumors that have self-renewal ability and can generate heterogeneous tumor cells. Cancer stem cells play an important role in tumor survival, proliferation, metastasis and recurrence. In essence, tumor stem cells maintain the vitality of tumor cell populations through self-renewal and unlimited proliferation; the movement and migration capabilities of tumor stem cells make the metastasis of tumor cells possible; tumor stem cells can be dormant for a long time and have a variety of resistance. Drug molecules are not sensitive to external physical and chemical factors that kill tumor cells, so tumors often recur after a period of time after conventional tumor treatment methods eliminate most common tumor ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/00A61K38/16A61P35/00G01N33/68G01N33/574
Inventor 罗瑞雪
Owner SUZHOU PULUODA BIOLOGICAL SCI & TECH
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