Drug target of tumor related diseases and application thereof

A tumor-related and drug-based technology, applied in the direction of anti-tumor drugs, drug combinations, pharmaceutical formulations, etc., can solve problems such as the unclear understanding of the mechanism of anti-tumor action

Inactive Publication Date: 2014-08-13
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

(Rajasubramaniam S, Vetrichelvan J, Yesim GP. Resorting chemotherapy and hormone therapy sensitivity by parthenolide in a xenograft hormone refratory protate cancer model. The Prostate, 2006, 66:1498-1511.) However, the current understanding of its anti-tumor mechanism Not yet clear, there are many different experimental results and hypotheses: NF-κB pathway, STAT pathway, JNK pathway, oxidative stress mechanism, etc.
(Pajak B, Gajkowska B, Orzechowski A. Molecular basis of parthenolide-dependent proapoptotic activity in cancer cells. Folia Histochem. Cytobiol., 2008; 46(2): 129-135.) The current anti-tumor effect of parthenolide There are different opinions on the mechanism, and it is urgent to use new research methods and means to clarify its clear target and mechanism

Method used

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  • Drug target of tumor related diseases and application thereof
  • Drug target of tumor related diseases and application thereof
  • Drug target of tumor related diseases and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Example 1: Preparation of EAH Sepharose4B-PTL affinity column and investigation of column parameters

[0022]Take 10ml of EAH Sepharose4B and mix with 15mg of parthenol (PTL) lactone, and shake the reaction overnight at room temperature in ethanol solution containing 50% triethylamine. The reaction solution was centrifuged at 3000 rpm for 3 minutes, and the supernatant was reserved for investigating the coupling rate. The column material was washed with triple-distilled water to remove the reaction solvent, and stored in 30 ml of 20% ethanol solution for later use. Another small amount of reacted column material was washed with acetone to remove water, and infrared identification was carried out. Utilize high-performance liquid chromatography to detect the prepared affinity column material, and calculate coupling amount and coupling rate according to the following formula:

[0023] Coupling amount (mg / ml) = (the amount of added PTL - the amount of uncoupled PTL) / volu...

Embodiment 2

[0026] Example 2: Searching for proteins specifically binding to parthenolide by a series of affinity chromatography

[0027] In this experiment, human pancreatic cancer cells PANC-1 were cultured in DMEM high-glucose medium containing 10% fetal bovine serum. After the cells grow to an appropriate number, discard the medium and gently wash with PBS twice, add NP40 cell lysate and lyse on ice for 30 minutes to obtain the cell lysate, centrifuge at 12000rpm at 4°C for 15min, collect the supernatant, and use it for pro- and chromatography. Take 1ml PANC-1 cell lysate and add 100μl affinity column, mix evenly, shake in ice bath and centrifuge (3000rpm, 1min, 0-4℃), take the column sediment for identification, add 100μl supernatant again Affinity column material, mix well, and shake for 40min. According to this method, five consecutive affinity reactions were carried out, and all reactions were carried out in an ice bath. The column precipitates obtained from the 5 reactions wer...

Embodiment 3

[0028] Example 3 A series of affinity chromatography to search for proteins specifically binding to parthenolide

[0029] Using the same method as in Example 2, cells from lung cancer (A549 cells, L78 cells, H460 cells), prostate cancer (PC-3 cells, DU145 cells), colorectal cancer (SW620 cells, LS513 cells), and bladder cancer were respectively cultured. Cancer (BIU-87 cells, 5637 cells, EJ cells), liver cancer (HepG2 cells, SMMC-7721 cells, Hep3b cells), nasopharyngeal carcinoma (C666-1 cells, CNE-1 cells), oral cancer (HB cells, KB Cell) ovarian cancer (A2780 cell, CAOV3 cell, SKOV-3 cell), cervical cancer (Hela cell), brain cancer (SF126 cell), neuroma (SH-SY5Y cell, M17 cell), lymphoma (DS-1 cell ), pancreatic cancer (BxPC-3 cells, SW1990 cells), gastric cancer (SGC7901 cells, MGC-803 cells), esophageal cancer (CaES-17 cells, Ec109 cells), laryngeal cancer (Hep-2 cells), tongue cancer (Tca8113 -P160 cells, TSCCA cells), breast cancer (MCF7 cells, A231 cells), skin cancer ...

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Abstract

The invention discloses an application of a human ribosomal protein L10 as a drug target for preventing and treating tumor related diseases. The amino acid sequence of the human ribosomal protein L10 is represented by the SEQ ID No.1. The human ribosomal protein L10 can be used as a drug target for in-vitro screening to prevent and treat tumor related diseases.

Description

technical field [0001] The invention relates to a tumor-related disease drug target and the use of specific binding compounds thereof. Background technique [0002] Cancer has become the second leading cause of death after cardiovascular disease. In recent years, with the rapid development of life science research, the understanding of the mechanism of malignant tumors has gradually deepened, and more and more new drug targets have been discovered. However, the mechanisms related to tumor cell growth, proliferation, metastasis and other processes and their drug resistance have not been fully elucidated. Therefore, the discovery and verification of specific antitumor drug targets is one of the hotspots in current scientific research. [0003] Ribosomal protein, referred to as "ribosomal protein", is a general term for all proteins involved in the formation of ribosomes, which form ribosomes in the form of non-covalent bonds with ribosomal RNA. There are currently 82 kinds ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/365A61P35/00
Inventor 刘楠陈依军刘欣
Owner CHINA PHARM UNIV
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