Eukaryotic recombinant protein specifically inhibiting stat3 activity and its preparation method and application

Abstract

The invention relates to a eukaryotic recombinant protein for specifically inhibiting the activity of STAT3, and a preparation method and an application thereof, and belongs to the field of medicine bioengineering. The full length of the eukaryotic recombinant protein for specifically inhibiting the activity of STAT3 comprises 210 amino acids, the No.1-No.25 amino acids are an NLS sequence, the No.26-No.31 amino acids are a His sequence, the No.34-No.199 amino acids are an MH2 sequence, the No.200-No.210 amino acids are a TAT sequence, and the His label sequence and the MH2 sequence are connected through two amino acids of KL. A competitive binding principle blocks ubiquitylation and degradation of PIAS3 and promotes binding of the PIAS3 and the STAT3, so the problem of difficulty in reaching of the expected effect and the expected safety of inhibition of activation of the STAT3 by present target inhibitors, RNA interference, antisense oligodeoxynucleotide and decoy oligonucleotide from the signal pathway perspective is solved, thereby proliferation of tumor cells is effectively inhibited, and the sensitivity of tumor stem cells to chemotherapeutics is promoted.

Description

technical field [0001] The invention relates to the field of medical bioengineering, in particular to a eukaryotic recombinant protein specifically inhibiting STAT3 activity, a preparation method and application thereof. Background technique [0002] In recent years, the theory of tumor stem cells (TSCs) has attracted more and more attention. At present, tumor stem cells have been successfully isolated from brain tumors, lung cancer, liver cancer, breast cancer, prostate cancer, colorectal cancer, skin cancer and other malignant tumors. The tumor stem cell hypothesis holds that tumor recurrence and metastasis after drug treatment are closely related to the survival of tumor stem cells. The proposal of cancer stem cells provides a reasonable explanation for the mechanism of tumor occurrence and recurrence, and is of great significance for the development of more effective anti-tumor drugs and the research of stem cells and cell biology. [0003] The Signal Transducer and Ac...

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Problems solved by technology

[0009] In view of the above problems, the present invention provides a eukaryotic recombinant protein that specifically inhibits STAT3 activity and its preparation method and application, so as to overcome the existing targeting inhibitors, RNA interference, antisense oligonucleotides and decoy oligonucleotides. Nucleotides, etc. inhibit the activation of STAT3 from the perspective of signaling pathways alone, but its effect and safety are difficult to meet expectations. Through the principle of competitive binding, the ubiquitination and degradation of PIAS3 are blocked and the combination of PIAS3 and STAT3 is promoted, thereby effectively inhibiting Proliferation of tumor cells, promoting the sensitivity of tumor stem cells to chemotherapeutic drugs

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