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Anti-tumor polypeptide Sur-X targeting to survivin-XIAP complex and application

A sur-x, anti-tumor technology, applied in the compound field of -XIAP, can solve the problems of increased risk of tumor recurrence and increased expression of XIAP, and achieve the effect of convenient clinical application

Active Publication Date: 2020-01-21
THE FIRST HOSPITAL OF CHINA MEDICIAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In patients with basal-like breast cancer, XIAP expression is elevated and the risk of tumor recurrence is significantly increased

Method used

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  • Anti-tumor polypeptide Sur-X targeting to survivin-XIAP complex and application
  • Anti-tumor polypeptide Sur-X targeting to survivin-XIAP complex and application
  • Anti-tumor polypeptide Sur-X targeting to survivin-XIAP complex and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Synthesis, purification and molecular weight determination of embodiment 1 polypeptide S

[0034] The anti-tumor polypeptide S of the present invention is obtained according to the specific amino acid sequence of survivin combined with XIAP reported in the previous literature, and the TAT transmembrane sequence is added to the amino terminal, and its final sequence is shown in SEQ ID No:1. A peptide segment that is not expressed in human cells is selected as a control for verifying that the polypeptide S of the present invention has a specific anti-tumor effect, which is denoted as polypeptide Con, and its final sequence is shown in SEQ ID No:2. Polypeptide NS is obtained by shortening polypeptide S, including two-thirds of the amino-terminal residues of S. The final sequence of NS is found in SEQ ID No:3. Polypeptides S, Con and NS were all synthesized by Fmoc solid-phase peptide synthesis method, which is briefly described as follows: according to the peptide sequenc...

Embodiment 2

[0037] Example 2 Observation under a confocal microscope that polypeptides can enter cells

[0038] Human colorectal cancer cells HCT116 and RKO were treated with Hoechst33342 at a ratio of 1:1000 and FITC-labeled polypeptide S and Con at a concentration of 10 μM for 1 h, and the entry of the polypeptide into the cells was observed under a confocal microscope.

[0039] image 3 Shown is the observation under the confocal microscope that both polypeptide S and Con can quickly enter the cell, indicating that polypeptide S has good membrane permeability.

Embodiment 3

[0040] Example 3 MTT detects the effect of S on the viability of human colorectal cancer cell lines HCT116 and RKO, human gastric cancer cell lines MGC-803 and MKN45, and human normal cell line SV5

[0041] Collect the cells in the logarithmic growth phase, count the cells and adjust the cell concentration, and inoculate 4000 cells / well in a 96-well culture plate; set the experimental group (S) and negative control group (Con), and set the concentration gradient for each group: 0, 2.5 μM, 5 μM, 10 μM, 15 μM, 20 μM, set 3 replicate wells for each concentration; after the cells adhered, give corresponding treatment, and incubate for 6h and 24h respectively; add 20μL MTT (5g / L) to each well, and incubate at 37°C After 4 hours, the supernatant was discarded, 200 μL dimethyl sulfoxide (DMSO) was added to each well, and the absorbance (OD) value at a wavelength of 570 nm was measured with a microplate reader; the relative cell viability at different concentrations was calculated; rep...

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PUM

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Abstract

The invention relates to the field of targeted treatment medicines for tumors and in particular relates to an anti-tumor polypeptide Sur-X targeting to a survivin-XIAP complex and application of the anti-tumor polypeptide Sur-X in treatment on multiple tumors including colorectal cancer and gastric cancer. The anti-tumor polypeptide Sur-X provided by the invention is capable of rapidly and efficiently inducing death of colorectal and gastric cancer cells by inhibiting formation of the survivin-XIAP complex, does not affect normal cells of human beings, and thus takes a treatment effect of specifically targeting to tumor cells. In addition, the polypeptide is easy to synthesize in vitro, and is convenient in clinical application. Therefore, the polypeptide Sur-X has potential commercial andindustrial value and can be widely used in the technical field of targeted treatment on tumors.

Description

technical field [0001] The present invention relates to the field of targeted therapeutic drugs for tumors, in particular to Sur-X, a polypeptide drug designed based on a survivin-XIAP complex, and their application in the treatment of various tumors including colorectal cancer and gastric cancer. In particular, it involves that Sur-X can promote tumor cell apoptosis and programmed necrosis by interfering with the formation of survivin-XIAP complex, and play the role of tumor targeting therapy. Background technique [0002] In recent decades, with the prolongation of the average life span of human beings, the change of living environment and lifestyle, cancer has become the number one killer threatening human life and health. Global Cancer Statistics (GLOBOCAN) results show that there were 18.1 million new cancer cases and 9.6 million cancer deaths in 2018. Among them, the incidence of colorectal cancer and gastric cancer ranked third and fifth respectively, and the sum of ...

Claims

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Application Information

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IPC IPC(8): C07K19/00A61K38/16A61K47/64A61P35/00
CPCA61K38/00A61P35/00C07K14/4747C07K14/82C07K2319/10
Inventor 车晓芳刘云鹏曲秀娟方婉侠
Owner THE FIRST HOSPITAL OF CHINA MEDICIAL UNIV
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