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Method for sensitizing BRAF inhibitor

A technology of inhibitors and genes, applied in the field of biomedicine, can solve the problems of drug resistance in melanoma patients

Inactive Publication Date: 2018-03-13
AFFILIATED HUSN HOSPITAL OF FUDAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Clinical practice shows that BRAF inhibitors in the treatment of melanoma have the characteristics of good tolerance, rapid onset of effect, and high treatment response rate. emergence of drug resistance

Method used

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  • Method for sensitizing BRAF inhibitor
  • Method for sensitizing BRAF inhibitor

Examples

Experimental program
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Effect test

Embodiment 1

[0012] Example 1 SOX4 gene knockdown enhances the killing effect of BRAF inhibitors on drug-resistant melanoma cell lines

[0013] The SOX4 gene is routinely knocked down; the classic method for detecting cytotoxicity, MTT, is used to detect the killing effect of BRAF inhibitors on drug-resistant melanoma cell lines after SOX4 gene knockdown. Pheni (PLX 10μM) A2058 cell viability decreased to 87%; SOX4shRNA gene knockdown cell viability decreased to 85%; SOX4shRNA gene knockdown combined with PLX 10μM cell viability decreased significantly to 54% (such as figure 1 shown), the results showed that SOX4 gene knockdown could enhance the killing effect of BRAF inhibitors on drug-resistant melanoma cell lines.

Embodiment 2

[0014] Example 2. SOX4 gene knockdown enhances the effect of BRAF inhibitors on drug-resistant melanoma cell lines inducing apoptosis

[0015] The SOX4 gene was routinely knocked down; the apoptosis of melanoma cell lines was detected by Annexin V and PI double-labeled flow cytometry. The apoptosis increased to 23.64%, and the middle and late apoptosis increased to 16.71%; the early apoptosis increased to 16.52%, and the middle and late apoptosis increased to 12.23% after SOX4shRNA gene knockdown; SOX4shRNA gene knockdown combined with PLX 10μM significantly increased the early apoptosis to 41.98%, and the mid-late stage apoptosis increased significantly to 29.41% (eg figure 2 shown), the results showed that SOX4 gene knockdown could enhance the apoptosis-inducing effect of BRAF inhibitors on drug-resistant melanoma cell lines.

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Abstract

The invention belongs to the field of biomedicine, and relates to a method for sensitizing a BRAF inhibitor. An SOX4 gene can be used to adjust the killing effect of a BRAF inhibitor on a drug resistant melanoma cell strain and can be taken as a maker of apoptosis-inducing effect of the BRAF inhibitor on the drug resistant melanoma cell strain. The SOX4 gene can be regulated, the expression of SOX4 is inhibited, the killing effect of the BRAF inhibitor on the drug resistant melanoma cell strain is enhanced, and the apoptosis-inducing effect of the BRAF inhibitor on the drug resistant melanomacell strain is also strengthened. Furthermore, the antitumor effect of the BRAF inhibitor can be enhanced by inhibiting the expression of SOX4.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to a sensitization method for BRAF inhibitors. The invention is based on the regulation of SOX4 gene, and increases the anti-tumor effect of BRAF inhibitors by inhibiting the expression of SOX4. Background technique [0002] The prior art discloses that melanoma is a malignant tumor derived from the skin, with a high degree of malignancy, and is prone to invasion and metastasis. According to relevant surveys, it is estimated that there will be 73,870 new cases of melanoma in the United States this year, and 9,940 people will die of melanoma. Although the incidence of melanoma in my country is relatively low, it has doubled in recent years, with about 20,000 new cases each year. In clinical practice, for patients with advanced melanoma, traditional treatment methods include: surgery, radiotherapy, chemotherapy and immunotherapy, but the efficacy is not satisfactory. Targeted therapy has bee...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K45/00A61K48/00A61K31/713A61P35/00C12N15/85C12N5/10
CPCA61K45/06A61K31/713A61K45/00C12N15/85C12N2800/107
Inventor 徐金华刘晓吴金峰程琼张耀华秦海红杜娟
Owner AFFILIATED HUSN HOSPITAL OF FUDAN UNIV
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