Application of metformin targeting COX6B2 in the preparation of drugs for the treatment of pancreatic cancer

A COX6B2 and metformin target technology, applied in the field of clinical medicine, can solve the problems of no cancer mechanism research, no expression in other normal tissues, etc., and achieve the effect of promoting pancreatic cancer metastasis

Active Publication Date: 2021-09-21
WENZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

At the same time, cytochrome c oxidase subunit 6B2 (COX6B2) is a subunit of the COX complex protein, which is specifically expressed in the testis, usually not expressed in other normal tissues, and found to be highly expressed in a variety of tumors, which may be involved in The process of tumor proliferation and metastasis, and it is worth noting that in the prior art, apart from metformin being the first-line oral drug for patients with type 2 diabetes mellitus (T2DM), there is no research on cancer-related mechanisms of action, especially how metformin affects the occurrence of PDAC The mechanism of action and development has not been reported so far

Method used

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  • Application of metformin targeting COX6B2 in the preparation of drugs for the treatment of pancreatic cancer
  • Application of metformin targeting COX6B2 in the preparation of drugs for the treatment of pancreatic cancer
  • Application of metformin targeting COX6B2 in the preparation of drugs for the treatment of pancreatic cancer

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Embodiment 1

[0040] Verification of the application of metformin targeting COX6B2 in the preparation of drugs for the treatment of pancreatic cancer

[0041] 1. Experimental content

[0042] 1. Construction of COX6B2 knock down cell line

[0043] 1.1 Annealing and identification of complementary DNA single strand

[0044] 1.1.1 DNA single-strand sequence

[0045] COX6B2 shRNA (SEQ ID NO: 1 and SEQ ID NO: 2) were designed by ourselves. The sequence was sent to Kebio Technology Company for synthesis.

[0046] SEQ ID NO: 1 is shown below:

[0047] 5'-GCAGCCCTGCGAGTACTATTT-3' (ORF region);

[0048] SEQ ID NO: 2 is shown below:

[0049] 5'-GCCTTCGAGTTCCTTGTTTCC-3'(3'-UTR region);

[0050] The above single chains were dissolved in deionized water according to the mother solution concentration of 1 μg / μL.

[0051] The shRNA is annealed, and the annealing system is shown in Table 1.

[0052] Table 1 DNA single strand annealing reaction system

[0053]

[0054] Annealing conditions: 90°C...

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Abstract

The invention discloses an application of metformin targeting COX6B2 in the preparation of a drug for treating pancreatic cancer (PDAC). Metformin reduces the level of mitochondrial oxidative phosphorylation through mitochondrial COX6B2, resulting in weakened energy metabolism of PDAC, thereby inhibiting the invasion and migration of PDCA cells. The present invention constructs different PDAC cell models, uses metformin to treat the PDAC cell lines, and discovers the mechanism of action between metformin, COX6B2, oxidative phosphorylation and PDAC. This discovery can not only provide effective molecular markers for the diagnosis of PDAC, It will also provide theoretical guidance for drug target design and drug selection for PDAC treatment, which has important clinical significance and social value.

Description

technical field [0001] The invention relates to the field of clinical medicine, in particular to the application of metformin targeting COX6B2 in the preparation of drugs for treating pancreatic cancer. Background technique [0002] Pancreatic cancer is a highly malignant tumor with a high mortality rate due to late diagnosis and poor prognosis. Even patients who have undergone curative resection have a high risk of disease recurrence due to tumor cell metastasis. Cancer testicular antigen is a testis-specific protein that is only present in testicular tissue but is found to be highly expressed in a variety of tumors. Mitochondria are the energy supply centers of cells and are critical to cell growth, division, migration, invasion, energy metabolism and apoptosis. Mitochondrial oxidative phosphorylation dysfunction can lead to dysfunction in multiple tissues, organs, and systems in the body, thereby causing some complex diseases, such as cancer, with high mortality and dis...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/155A61P1/18A61P35/00C12N15/867C12N5/10C12Q1/02
CPCA61K31/155A61P1/18A61P35/00C12N5/0676C12N5/0693C12N15/86C12N2503/02C12N2510/00C12N2740/15043C12N2800/107G01N33/5011G01N33/507G01N2500/10
Inventor 方合志沈丽君吴旭聪聂珂李晋王雨晴
Owner WENZHOU MEDICAL UNIV
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