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Application of GRP78 gene in drug for improving chemotherapy sensitivity of tumor stem cells

A cancer stem cell and sensitivity technology, which is applied in the application field of GRP78 gene in improving the chemosensitivity of cancer stem cells, can solve the problem of unclear key role of cancer stem cells in chemoresistance, reduce the ability of stem cells to form spheroids, and improve the quality of life. , enhance the effect of curative effect

Inactive Publication Date: 2018-05-08
GUANGDONG HOSPITAL OF TRADITIONAL CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the key role of GRP78 in cancer stem cell chemotherapy resistance is still unclear, and there is no targeted drug designed for GRP78.

Method used

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  • Application of GRP78 gene in drug for improving chemotherapy sensitivity of tumor stem cells
  • Application of GRP78 gene in drug for improving chemotherapy sensitivity of tumor stem cells
  • Application of GRP78 gene in drug for improving chemotherapy sensitivity of tumor stem cells

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Example 1: Chemotherapy can induce increased expression of GRP78, β-catenin and ABCG2 in vivo and in vitro in breast cancer cells

[0037] In order to detect the impact of chemotherapy on the expression level of GRP78, the present invention detected the responses of human breast cancer cell lines MCF-7 and MDA-MB-231 to three first-line breast cancer chemotherapy drugs (epirubicin, paclitaxel and 5-fluorouracil) . The results of Western blotting showed that after treatment with chemotherapeutic drugs, the expression levels of GRP78 in the two breast cancer cells were significantly increased, and the levels of β-catenin and ABCG2 were also increased in a dose-dependent manner ( figure 1 A and B in), suggesting that GRP78 gene may be related to chemotherapy response and ABCG2 expression. In the next step, in order to verify the change trend of the expression level of GRP78 after chemotherapy in vivo, a nude mouse model was used in this example to inoculate two kinds of b...

Embodiment 2

[0038] Example 2 GRP78 gene is enriched and expressed on breast cancer stem cells

[0039] Based on the findings in Example 1, in order to study the relationship between the GRP78 gene and chemotherapy responsiveness, the chemotherapy sensitivity of human breast cancer cell MCF-7 and its drug-resistant cell MCF-7 / ADR was first detected. It was found that in MCF-7 / ADR cells, the proportion of side group cells was significantly increased ( figure 2 in A). At the same time, the results of flow cytometry indicated that drug-resistant cells also significantly increased the ability to pump out chemotherapeutic drugs ( figure 2 in B). In order to explore the expression status of GRP78 gene in drug-resistant cells, MCF-7 and its drug-resistant cells were detected by western blotting, and the results indicated that the level of GRP78 gene in drug-resistant cells was significantly increased. Accompanied by the up-regulation of ABCG2 and β-catenin expression, it further illustrates ...

Embodiment 3

[0040] Example 3 GRP78 gene suppression reduces breast cancer stem cell drug resistance and promotes its differentiation

[0041] In order to further study the role of GRP78 gene in regulating the drug resistance of breast cancer cells, the present invention uses GRP78siRNA to silence the expression of GRP78 gene in MCF-7 / ADR cells, and then sorts out stem cells before and after siRNA interference to detect the proportion of side population cells. The results showed that after GRP78siRNA was applied, the proportion of side population cells in breast cancer stem cells decreased from 22.5% to 7.5% ( image 3 A in A), meanwhile, the content of epirubicin in the cells was significantly increased ( image 3 in B), accompanied by decreased expression levels of β-catenin and ABCG2 ( image 3 in C). The results of the study suggest that GRP78 gene is an effective factor regulating drug resistance of breast cancer stem cells, and its mechanism is closely related to β-catenin and ABCG...

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Abstract

The invention relates to the field of chemotherapy of tumor stem cells, in particular to application of a GRP78 gene in a drug for improving chemotherapy sensitivity of tumor stem cells as well as a screening method adopting the GRP78 gene as an effect target inhibitor. The effect target of the inhibitor is the GRP78 gene, the GRP78 gene is correlated to the drug-resisting characteristics of the tumor stem cells, and the inhibitor inhibits the expression of GRP78 gene in the tumor stem cells, so that the content of a chemotherapy drug in the tumor stem cells is increased, and the chemotherapysensitivity of the tumor stem cells can be improved. By adopting the application of the GRP78 gene, the sensitivity of the tumor stem cells to the chemotherapy drug can be improved, the curative effect of the chemotherapy drug can be improved, the lifetime of a tumor patient can be prolonged, a chemotherapy response rate of the tumor patient can be increased, and a potential and good application prospect in the drug for improving the chemotherapy sensitivity of the tumor stem cells can be realized.

Description

technical field [0001] The invention relates to the field of tumor stem cell chemotherapy, in particular to the application of GRP78 gene in improving the chemotherapy sensitivity of tumor stem cells. Background technique [0002] Malignant tumors are one of the major diseases that threaten human health and life. According to statistics from the International Agency for Research on Cancer, there were about 14.1 million new cancer cases and 8.2 million cancer deaths worldwide in 2012, compared with 12.7 million and 7.6 million in 2008. Morbidity and mortality are on the rise. At the same time, statistics show that 80% of new tumors in the world occur in developing countries such as China, India, and Brazil. In my country, malignant tumors have surpassed cardiovascular and cerebrovascular diseases, and have become the number one cause of death among Chinese residents, accounting for 10% of the total number of deaths. The percentage has risen from around 13% in the 1970s to ov...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K31/53A61K31/546A61K31/58A61K31/496A61K31/5377A61K31/517A61K31/505A61K31/55A61K31/7076A61K31/352A61K31/7034A61K31/46A61P35/00G01N21/552
CPCA61K45/00A61K31/352A61K31/46A61K31/496A61K31/505A61K31/517A61K31/53A61K31/5377A61K31/546A61K31/55A61K31/58A61K31/7034A61K31/7076G01N21/553
Inventor 王志宇王能郑轶枫王胜奇
Owner GUANGDONG HOSPITAL OF TRADITIONAL CHINESE MEDICINE
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