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Composition for treatment or metastasis suppression of cancers which includes P34 expression inhibitor or activity inhibitor as active ingredient

一种活性抑制剂、有效成分的技术,应用在治疗癌或抑制癌转移的组合物领域,能够解决未能提出可根治癌症治疗方法、没有治疗方法、副作用大等问题,达到肿瘤发生率及集落形成能力减少的效果

Active Publication Date: 2016-01-27
THE ASAN FOUND +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the case of early detection of cancer, treatment methods such as surgery, radiation therapy, and chemotherapy can be used, but there is a problem of large side effects. In the case of advanced cancer or cancer metastasis, there is no special treatment method, and only in advanced cancer In the countdown of life, the life is gradually ending
[0003] Recently, various biochemical mechanisms related to cancer have been clarified, and various therapeutic agents have been developed accordingly, but until now, no cure for cancer has been proposed

Method used

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  • Composition for treatment or metastasis suppression of cancers which includes P34 expression inhibitor or activity inhibitor as active ingredient
  • Composition for treatment or metastasis suppression of cancers which includes P34 expression inhibitor or activity inhibitor as active ingredient
  • Composition for treatment or metastasis suppression of cancers which includes P34 expression inhibitor or activity inhibitor as active ingredient

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0127] Example 1. Analysis of the interaction between p34 and NEDD4-1 in vivo and in test tubes and the impact of p34 on the stability of NEDD4-1 protein

[0128] 1-1. Analysis of the interaction between endogenous p34 and NEDD4-1

[0129] (1) In order to identify proteins interacting with NEDD4-1, co-immunoprecipitation, tandem affinity purification, and mass analysis were performed from cell lysates using an antibody against NEDD4-1 protein. First, in order to perform co-immunoprecipitation, after mixing the lysates of 293 cells (HEK293 cells), DU145 cells as prostate cancer cells, and MCF7 cells as breast cancer cells with anti-NEDD4-1 antibody, the temperature of 4°C Incubate for 12 hours. Next, 20 μl of Protein A / GPlus-Sepharosebeads (Santa Cruz Biotechnology, Santa Cruz, CA, USA) was added to the above culture and mixed, followed by additional culture for 2 hours. The acquired immunoprecipitate was washed 5 times with lysis buffer (nonidetP-40lysis buffer), followed by...

Embodiment 2

[0165] Example 2. Analysis of the effect of p34 on the regulation of polyubiquitination of the homologous phosphatase-tensin mediated by NEDD4-1

[0166] (1) Use p34 deoxyribonucleic acid to analyze the silencing effect of p34 due to inhibition of expression (p34-deoxyribonucleic acid: I: 5'-GCAAGGGUCUGAAGCGGAA-3, II: 5'-GGAAACGGGAGGAGGAGGA-3', III: 5'-CCGAAUUGGACUACCUCAU -3'). After MDA-MB-231 and MCF7 cells were transfected with p34-deoxyribonucleic acid, the expression levels of each protein were analyzed by Western blotting. exist Figure 16 The experimental results are shown in .

[0167] Such as Figure 16 As shown, it was confirmed that p34-DNA induced an increase in the expression of the homologous phosphatase-tensin and a decrease in the expression of p-protein kinase B in a concentration-dependent manner.

[0168] Furthermore, after the 293 cells and mouse embryonic fibroblast cells were transfected with green fluorescent protein-labeled p34, the expression level...

Embodiment 3

[0198] Example 3. Analysis of regulation of monopolyubiquitination and polyubiquitination of the NEDD4-1 homologous phosphatase-tensin by p34

[0199] (1) Recently, NEDD4-1 not only mediates the in vitro and intracellular polyubiquitination of the homologous phosphatase-tensin, but also mediates the monoubiquitination, monoubiquitination of the homologous phosphatase-tensin The nuclear movement (nuclear import) (Wang et al., 2007) of the mediator through the nuclear membrane pore of homologous phosphatase-tensin, as shown in Example 2 above, confirms that p34 regulates homologous phosphatase-tensin through NEDD4-1 Polyubiquitination. Based on the above results, the present inventors analyzed the effect of p34 on the production of monoubiquitination of the homologous phosphatase-tensin.

[0200] First, four cancer cell lines expressing p34 and NEDD4-1 (MCF7, MDA-MB231, DU145 cells and LS1034) were transfected into p34-deoxyribonucleic acid through intrinsic-cellubiquitination ...

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Abstract

The present invention relates to a composition for treatment or metastasis suppression of cancers which includes a p34 expression inhibitor or activity inhibitor as an active ingredient. According to the present invention, the p34 protein knock-down causes monoubiquitination of PTEN and accordingly nuclear localization of PTEN is induced, as a result, an Akt pathway which is related to survival, proliferation, invasive properties and metastatic properties of tumours is inhibited, and thus there is an effect of significantly reducing clonogenic potential and tumour forming potential of various cancer cells which simultaneously express PTEN and NEDD4-1. Consequently, the p34 gene expression inhibitor or p34 protein activity inhibitor according to the present invention can be effectively used as a treatment agent or a metastasis suppression agent for cancers.

Description

technical field [0001] The present invention relates to a composition for treating cancer or suppressing cancer metastasis comprising an expression inhibitor or activity inhibitor of P34 as an active ingredient. Background technique [0002] Cancer is one of the biggest diseases that endanger human health. It is a disease that occurs when cells proliferate in an unlimited and unadjustable way without dying through a series of mutation processes. Causes of cancer can include environmental or extrinsic causes such as chemicals, viruses, bacteria, and ionizing radiation, and intrinsic causes such as congenital gene mutations (Klaunig & Kamendulis, AnnuRev Pharmacol Toxicol., 44:239-267, 2004). In the case of early detection of cancer, treatment methods such as surgery, radiation therapy, and chemotherapy can be used, but there is a problem of large side effects. In the case of advanced cancer or cancer metastasis, there is no special treatment method, and only in advanced cance...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00C12N15/113A61P35/00
CPCC12N15/113C12N2310/11C12N2310/12C12N2310/14A23L33/13A61K31/4245A61P35/00A61P35/02A61P35/04A61P43/00A23V2002/00C12N15/1137C12N2310/122C12N2310/531C12Q1/6886C12Q2600/136C12Q2600/158G01N33/5011
Inventor 金太源陈东勳弘承祐文哉喜申在植金珍善郑景娥李政慎崔恩卿李在链洪镕祥金圭杓南基烨金峰徹
Owner THE ASAN FOUND
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