Application of Wwox as drug target for prevention and treatment of cancer

A technology of medicine, use, applied in the fields of molecular biology and biomedicine

Pending Publication Date: 2019-09-20
SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, there is no mature tumor-targeted treatment method for STAT3 signaling pathway in this field, so there is an urgent need to develop specific targets for the prevention or treatment of cancer

Method used

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  • Application of Wwox as drug target for prevention and treatment of cancer
  • Application of Wwox as drug target for prevention and treatment of cancer
  • Application of Wwox as drug target for prevention and treatment of cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0196] Example 1. Detection of Wwox in breast cancer cell lines and breast cancer patient samples

[0197] In order to explore the expression of Wwox and p-STAT3 in breast cancer, the inventors detected 12 kinds of breast cancer cells by Western method, and found that Wwox was highly expressed in Luminal breast cancer cells, while STAT3 was lowly expressed. In basal-like breast cancer cells, STAT3 is highly activated, while Wwox is in a low expression state ( figure 1 a).

[0198] Moreover, overexpression of Wwox in Basal-like breast cancer cell lines (SUM159, HBL100, MDA-MB-231) can significantly reduce the phosphorylation level of STAT3 ( figure 1 b).

[0199] In addition, the inventor detected the expression levels of Wwox and p-STAT3 in 90 samples of triple-negative breast cancer patients by immunohistochemistry, and found that the expression of Wwox could not be detected in almost all samples of triple-negative breast cancer, while the activation of STAT3 The level was...

Embodiment 2

[0201] Example 2, Wwox can inhibit the metastasis and growth of breast cancer cells

[0202] In order to study the role of Wwox in the process of breast cancer, the inventors first found through Tranwell migration assay that overexpressing Wwox in Basal-like breast cancer cells (SUM159, MDA-MB-231) could significantly inhibit the migration ability of cells ( figure 2 a, b).

[0203] Next, the inventors observed the effect of Wwox on the proliferation and metastasis of breast cancer in vivo through mammary fat pad in situ. By injecting MDA-MB-231 control cells and Wwox overexpression cells in vivo, it was found that Wwox can significantly inhibit the growth of tumors, the size of tumors was significantly reduced, and the number of liver metastases of tumors was also significantly reduced. The above experiments in vivo and in vitro have proved that Wwox can significantly inhibit the metastasis of breast cancer ( figure 2 c-h).

[0204] In order to study the direct evidence ...

Embodiment 3

[0205] Example 3, Wwox interacts with STAT3 through a specific domain

[0206] According to the above research results, the inventors believe that there may also be an interaction between Wwox and STAT3, and the exogenous Wwox and STAT3 were overexpressed in 293T cells by co-immunoprecipitation (IP) experiments ( image 3 a), to prove that there is an interaction between the two.

[0207] Further through IP experiments, it was found that in MCF-10A, MCF-7 and T47D cells, there was also an interaction between endogenous STAT3 and Wwox ( image 3 b).

[0208] The inventor constructs and expresses different fragments of Wwox and STAT3 respectively, and the establishment of the truncated body is as follows image 3 c, f, overexpressed in 293T cells (here which specific cell is overexpressed). It was found by immunoprecipitation experiments that Wwox interacts with STAT3 through the WW1 domain (present in positions 1 to 54 in SEQ ID NO: 2) ( image 3 c, d), while STAT3 interact...

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Abstract

The invention relates to an application of Wwox as a drug target for prevention and treatment of cancer. The invention discloses that the expression of Wwox is negatively correlated with the activation level of STAT3 for the first time. On one hand, the Wwox can inhibit the phosphorylation of JAK2, on the other hand, the Wwox can inhibit the binding ability of JAK2 and STAT3 and then inhibit the phosphorylation of STAT3 through the action with JAK2. In addition, the Wwox can also inhibit the expression of IL-6 through STAT3, and the level of the Wwox expression quantity has a significant correlation in the prognosis of breast cancer patients. Therefore, the Wwox plays a quite important role in tumor, especially breast cancer, and is a target for cancer treatment.

Description

technical field [0001] The invention belongs to the fields of molecular biology and biomedicine, in particular, the invention relates to the application of Wwox as a drug target for preventing and treating cancer. Background technique [0002] Malignant tumor is a complex disease with unknown etiology, which seriously threatens human life and health. In China, the incidence and mortality of tumors are significantly higher than the world average. Under the action of hereditary and carcinogenic factors, the DNA damage and mutation of the genetic material of normal cells are caused, and at the same time, it is accompanied by the activation of various oncogenes and the inactivation of tumor suppressor genes, making cancer cells grow and proliferate uncontrollably. Adjacent to normal tissues, metastasized to distant tissues and organs. For example, breast cancer is a malignant and heterogeneous tumor occurring in the mammary glandular epithelium, with different clinical manifes...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/02G01N33/574
CPCC12Q1/6886G01N33/57415G01N33/5011C12Q2600/136C12Q2600/158
Inventor 詹丽杏常人绪宋乐乐
Owner SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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