Application of CDO1 in preparing stomach cancer treating drug associated with ferroptosis

A therapeutic drug, CDO1 technology, applied in the field of function and application of genes and proteins, can solve problems such as unclear effects

Inactive Publication Date: 2018-04-10
NANFANG HOSPITAL OF SOUTHERN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the role of CDO1-induced changes in cysteine ​​metabolism in gastric cancer cell ferroptosis is still unclear, and further research is urgently needed

Method used

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  • Application of CDO1 in preparing stomach cancer treating drug associated with ferroptosis
  • Application of CDO1 in preparing stomach cancer treating drug associated with ferroptosis
  • Application of CDO1 in preparing stomach cancer treating drug associated with ferroptosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0086] Example 1: Erastin induces ferroptosis in gastric cancer cells.

[0087] In order to verify whether Erastin can induce ferroptosis in human gastric cancer cells, human gastric cancer cell lines AGS and BGC823 were treated with different concentrations of Erastin (0, 5, 10, 15, 20 μg / ml), and the proliferation activity of the cells was detected by MTT assay after 24 hours . The results showed that with the increase of Erastin stimulation concentration, the growth inhibition rate of human gastric cancer cells gradually increased ( Figure 1A ), and this growth inhibition (under stimulation of 10 μg / ml Erastin) can and can only be reversed by the ferrostain-1andliprostatin-1 inhibitor, while the apoptosis inhibitor ZVAD-FMK, autophagy inhibitor 3-Methyladenine, necrosis inhibitor The effect of necrostatin was not statistically significant ( Figure 1B ). According to the above experimental results, it is believed that Erastin can induce ferroptosis in gastric cancer cell...

Embodiment 2

[0088] Example 2: The expression profile of CDO1 in gastric cancer cells and tissues.

[0089] In order to explore the expression level of CDO1 in gastric cancer cells, six human gastric cancer cell lines and immortalized human gastric mucosal epithelial cells GES-1 were collected to detect their mRNA and protein expression levels ( Figure 2A and 2B ). The results of q-PCR and Western blot both showed that the expression of CDO1 was low in gastric cancer cells and high in GES-1 cells.

[0090] For gastric cancer tissues, 16 pairs of surgical specimens from patients with clinically diagnosed gastric cancer were taken to detect the mRNA expression level ( Figure 2C ), the results showed that the expression of CDO1 in gastric cancer specimens was generally lower than that in paracancerous specimens. Four pairs of surgical specimens from gastric cancer patients were further selected to detect their protein expression levels. The results of Western blot also indicated that the...

Embodiment 3

[0091] Example 3: Overexpression of CDO1 promotes ferroptosis in gastric cancer cells.

[0092] In order to clarify the role of CDO1 in the process of gastric cancer cell ferroptosis, the overexpressed CDO1 plasmid was transfected into AGS and BGC823 cell lines by transient transfection, and then stimulated with different concentrations of Erastin (0, 10, 20ug / ml). The results of MTT experiments showed that overexpression of CDO1 could promote the process of Erastin-induced ferroptosis in gastric cancer cells ( Figure 1D ).

[0093] Current studies have shown that Erastin leads to a series of ferroptosis events by inhibiting the uptake of cysteine ​​in cells, including GSH deficiency, GPX4 inactivation, ROS accumulation and changes in mitochondrial morphology. In order to further explore the effect of overexpression of CDO1 on ferroptosis, AGS and BGC823 human gastric cancer cell lines overexpressing CDO1 were treated with 10 μg / ml Erastin, and DMSO was used as control to st...

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Abstract

The invention belongs to the field of functions and applications of genes and proteins, and relates to the application of CDO1 in the preparation of gastric cancer treatment drugs related to ferroptosis. The invention provides a new application of CDO1, and the new application is that CDO1 is used in the preparation of gastric cancer treatment drugs related to ferroptosis. The invention provides that the agent capable of inducing ferroptosis in gastric cancer cells is Erastin. The present invention also provides that the promoter of gastric cancer cell ferroptosis process is overexpression of CDO1 plasmid. The present invention reveals for the first time the mechanism of CDO1 regulating cysteine ​​metabolism in Erastin-induced gastric cancer cell ferroptosis and the transcriptional regulation of c-Myb on CDO1 expression during ferroptosis. CDO1 is an important part of the c-Myb signaling pathway in gastric cancer and an important metabolic node in the process of ferroptosis. Overexpression of CDO1 can promote the process of ferroptosis in gastric cancer cells. Therefore, the present invention provides a theoretical basis for the study of gastric cancer treatment based on ferroptosis, and provides an insertion point for the preparation of new gastric cancer treatment drugs.

Description

technical field [0001] The invention belongs to the field of functions and applications of genes and proteins, and relates to the metabolic application of CDO1, in particular to the application of CDO1 in the preparation of gastric cancer treatment drugs related to ferroptosis. Background technique [0002] Gastric cancer is the second most lethal malignancy worldwide. In China, although the incidence of gastric cancer in urban residents is on a downward trend, its mortality rate still ranks third in the order of malignant tumors, posing a serious threat to people's health. Surgical resection is currently the only way to cure gastric cancer, but more than two-thirds of gastric cancer patients are diagnosed at an advanced stage, missing the best time for radical surgical treatment. At present, there are various kinds of chemotherapy drugs for gastric cancer, and the chemotherapy regimens for advanced gastric cancer have also been continuously improved in the development of m...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61P35/00
CPCA61K45/00
Inventor 石敏郝诗慧赵洋
Owner NANFANG HOSPITAL OF SOUTHERN MEDICAL UNIV
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