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Application of TPCA-1 in precise prevention and treatment of tumors related to Svv circular regulatory pathways

A TPCA-1, 1.TPCA-1 technology, applied in the field of cancer and tumors, can solve problems such as no tumor research reports, and achieve the effect of reducing the expression of Svv

Inactive Publication Date: 2019-06-25
粤北人民医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, whether this positive regulation mechanism exists in other common tumor cells, and whether it may form a positive regulatory loop of Svv→IKKβ→NF-κB→Svv through positive regulation of NFkB by Svv has not been reported.
[0012] (2) There is still no definite answer to the transcriptional regulation mechanism of Svv as a transcription factor, and how it maintains self-expression from scratch, from weak to strong and sustained high expression
[0013] (3) There is no research report on the use of TPCA-1 in the precise prevention and treatment of tumors related to the positive regulatory loop of Svv→IKKβ→NF-κB→Svv

Method used

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  • Application of TPCA-1 in precise prevention and treatment of tumors related to Svv circular regulatory pathways
  • Application of TPCA-1 in precise prevention and treatment of tumors related to Svv circular regulatory pathways
  • Application of TPCA-1 in precise prevention and treatment of tumors related to Svv circular regulatory pathways

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] In esophageal squamous cell carcinoma ECA-109 cell line, we observed that exogenous Svv up-regulates endogenous Svv protein level through IKKβ. The specific performance is:

[0030] 1. Exogenous Svv significantly increased the expression of endogenous Svv ( Figure 5 b);

[0031]2. The IKKβ-specific inhibitor TPCA-1 reduced the expression of endogenous Svv, and the level of Svv mRNA was down-regulated by 70% as detected by qPCR ( Figure 5 a).

[0032] The specific experimental method is as follows:

[0033] 1.3×flag-Survivin-GV-219 plasmid construction, transformation, extraction and sequencing

[0034] 1.1.3×flag-Survivin, 3×flag-p107 primer design and amplification

[0035] (1) Design PCR primers according to the Survivin (HM625836.1, GI:30436781) coding sequence in GenBank, and introduce an XhoI restriction site at the 5' end of the upstream primer, and a KpnI restriction site at the 5' end of the downstream primer, and design primers Add a 3×flag tag recognit...

Embodiment 2

[0080] Using the same method as in Example 1, we observed in the lung adenocarcinoma cell line (SPC-A-1):

[0081] 1. Exogenous Svv significantly increased the expression of endogenous Svv ( Figure 6 a Swimming band 3), and also increased the expression of IKKβ ( Figure 6 b swim belt 3);

[0082] 2. The IKKβ-specific inhibitor TPCA-1 is reducing the expression of IKKβ ( Figure 6 b Swimming band 4) at the same time, also reduced the expression of endogenous Svv ( Figure 6 a swim belt 4).

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Abstract

The invention provides application of an IKKBeta kinase inhibitor-TPCA-1 in accurate prevention and treatment of tumors. TPCA-1 blocks an Svv-IKKBeta-NF-kB-Svv circulating regulation and control pathway in tumor tissue by specifically inhibiting IKKBeta expression, finally remarkably reduces the expression of the Svv and further inhibits the occurrence and progress of tumors; As a very important proto-oncogene, Svv is continuously highly expressed in almost all tumor tissues, the Svv-IKKBeta-NF-kB-Svv circulating regulation and control pathway exists widely in many kinds of tumor cells, so TPCA-1 has the prospect of accurate prevention and treatment of tumors associated with Svv-IKKBeta-NF-kB-Svv circulating regulation and control pathways.

Description

technical field [0001] The present invention relates to the field of precise prevention and treatment of tumors, and specifically relates to a compound that can significantly inhibit the expression of Svv by blocking the Svv→IKKβ→NF-κB→Svv cycle regulation pathway in tumor tissue cells—IKKβ kinase specific inhibitor TPCA- 1. Use in precise prevention and treatment of tumors related to the Svv→IKKβ→NF-κB→Svv cycle regulation pathway. Background of the invention [0002] Structural and functional characteristics of Survivin (Svv): The coding gene of Svv, BIRC5, is located on human chromosome 17q25 and consists of three introns and four exons [29] . Svv is the smallest member of the IAPs family. The wild-type Svv consists of 142 amino acids and usually exists in the form of homodimers in the cytoplasm. A number of studies have shown that Svv can interact with a variety of intrinsic and extrinsic apoptosis regulators, and significantly inhibit the occurrence of apoptosis. At ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/381A61P35/00
Inventor 李惠武李卉喻亮刘玲李颖
Owner 粤北人民医院
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