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Application of high expression of recql4 gene as a target in the preparation of anti-gastric cancer drugs

A technology for gene suppression and gastric cancer, applied in the fields of biochemistry and molecular biology, can solve the problem that the relationship between the expression of gastric cancer and the chemosensitivity of gastric cancer has not been reported.

Active Publication Date: 2019-07-26
BEIJING INST OF GENOMICS CHINESE ACAD OF SCI CHINA NAT CENT FOR BIOINFORMATION
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Studies have shown that the RecQL4 gene is abnormally highly expressed in osteoblastoma (Maire G, Neoplasia.2009), breast cancer (Fang HB, PLoSOne.2013) and prostate cancer (Su Y, Cancer Res.2010), but its The expression in gastric cancer and its relationship with drug resistance and chemosensitivity of gastric cancer have not been reported

Method used

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  • Application of high expression of recql4 gene as a target in the preparation of anti-gastric cancer drugs
  • Application of high expression of recql4 gene as a target in the preparation of anti-gastric cancer drugs
  • Application of high expression of recql4 gene as a target in the preparation of anti-gastric cancer drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1 Abnormally high expression of RecQL4 gene in gastric cancer cells and clinical tissues

[0039] This embodiment detected the expression level of RecQL4 protein in 7 strains of gastric cancer cells (MGC-803, AGS, HGC-27, MKN45, NCI-N87, SUN-1, SNU-16), and found that in all 7 strains of gastric cancer cells, RecQL4 Protein expression levels were significantly higher than those of the control samples ( figure 1 ). Subsequently, 11 pairs of gastric cancer clinical samples and paracancerous controls were collected to detect the expression of RecQL4 protein, and it was found that the expression level of RecQL4 in 8 pairs of gastric cancer samples was significantly higher than that of paracancerous samples among the 11 pairs of clinical samples ( figure 2 ). The above results indicated that the expression of RecQL4 gene was significantly increased in gastric cancer.

Embodiment 2

[0040] Example 2 The expression level of RecQL4 is closely related to the drug resistance of gastric cancer cells

[0041] In order to detect the correlation between RecQL4 and gastric cancer cell drug resistance, this example detected the sensitivity of 7 gastric cancer cell lines to the clinical first-line chemotherapy drug cisplatin, and the results showed that gastric cancer cells with relatively high expression of RecQL4 (AGS, NCI-N87, SNU- 16) The resistance to cisplatin is also relatively high, while gastric cancer cells (SNU-1, MGC-803) with relatively low expression of RecQL4 are also relatively sensitive to cisplatin ( image 3 ). Although MKN45 cells with relatively low expression of RecQL4 and HGC-27 cells with relatively high expression of RecQL4 showed relatively moderate cisplatin resistance, the overall resistance trend still clearly shows that the expression level of RecQL4 is closely related to the response of gastric cancer cells to cisplatin. Platinum resi...

Embodiment 3

[0042] Example 3 RecQL4 enhances gastric cancer cell resistance to cisplatin

[0043] In order to further verify the relationship between RecQL4 and the drug resistance of gastric cancer cells, in this example, 3 strains of gastric cancer cells (MKN45, SUN-1, MGC-803) with relatively low expression of RecQL4 were used to make the 3 strains by transfecting expression plasmids containing the RecQL4 gene. The expression level of RecQL4 in strain cells was significantly increased ( Figure 4 Upper), and then detect whether the cells are resistant to cisplatin after the expression of RecQL4 is increased. The results showed that when the expression level of RecQL4 increased, the resistance of cells to cisplatin also increased significantly ( Figure 4 Down). Then three gastric cancer cell lines with relatively high expression of RecQL4 (NCI-N87, AGS, HGC-27) were used to inhibit the expression of RecQL4 by adenovirus infection, and the resistance of gastric cancer cells to cisplat...

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Abstract

The invention discloses application of a highly-expressed RecQL4 gene as a target spot in preparing anti-gastric-cancer drugs, and relates to the application of the RecQL4 gene as a new molecular marker in predicating chemotherapy sensitivity and prognostic evaluation of gastric cancer. According to the application, the expression level of the RecQL4 is firstly found to be highly consistent with drug resistance, to a chemotherapeutic first-line drug cis-platinum, of gastric cancer cells; a RecQL4 gene inhibitor can be used as an active ingredient in the anti-gastric-cancer drugs; the inhibitor also can be combined with platinum drugs for gastric cancer treatment; besides, the expression level of the RecQL4 can be used as an independent molecular mark for predicating the sensitivity and the prognosis, to chemotherapeutic drugs, of the gastric cancer. The application provides guiding significance in predicating the drug resistance and the prognosis of the chemotherapy for the gastric cancer, and creates new standards for clinically guiding pharmacy and carrying out prognostic evaluation.

Description

technical field [0001] The invention relates to the fields of biochemistry and molecular biology, in particular to the application of the high expression of RecQL4 gene as a target in the preparation of anti-gastric cancer drugs. Background technique [0002] The morbidity and mortality rate of gastric cancer ranks second among all cancers and has an increasing trend year by year. The current clinical treatment for gastric cancer is mainly based on platinum-based chemotherapy, but even for patients of the same type and onset period There will also be significant differences in treatment effects (Shah MA.J Clin Oncol.2015). At the same time, during the course of clinical chemotherapy, patients with gastric cancer often develop resistance to chemotherapy drugs, which eventually leads to a significant decline in the therapeutic effect. Therefore, how to better predict the sensitivity of gastric cancer to chemotherapy drugs such as cisplatin is of great significance for the cli...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K48/00A61K33/243A61P35/00C12Q1/6886A61K31/7105
CPCA61K31/7105A61K33/24C12Q1/6886C12Q2600/106C12Q2600/118C12Q2600/158A61K2300/00
Inventor 赵永良默董亮方洪波魏迪
Owner BEIJING INST OF GENOMICS CHINESE ACAD OF SCI CHINA NAT CENT FOR BIOINFORMATION