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Application of ceritinib in preparation of tumor chemotherapy drug sensitizer and antitumor pharmaceutical composition

A technology of anti-tumor drugs and chemotherapy drugs, applied in the field of medicine

Inactive Publication Date: 2017-11-07
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is no literature reporting that ceritinib combined with anti-tumor chemotherapy drugs can reverse the killing of tumor cells on chemotherapy drugs

Method used

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  • Application of ceritinib in preparation of tumor chemotherapy drug sensitizer and antitumor pharmaceutical composition
  • Application of ceritinib in preparation of tumor chemotherapy drug sensitizer and antitumor pharmaceutical composition
  • Application of ceritinib in preparation of tumor chemotherapy drug sensitizer and antitumor pharmaceutical composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] The killing effect of chemotherapy drugs on drug-resistant cell line SK-cbt-2 and its parental SK-hep-1.

[0036] (1) Experimental method

[0037] SK-cbt-2 was inoculated on 100mm culture dishes, cultured for 72 hours, and the culture medium was removed; digested with 0.25% trypsin, collected cells, counted cells, prepared a single cell suspension with a concentration of 20,000 cells / ml, and inoculated 0.2ml single cells in each well. The cell suspension was transferred to a 96-well plate, and the total number of cells per well was 4000; cultured overnight, and the corresponding chemotherapeutic drugs were added for treatment; the treatment concentration of docetaxel was 0, 0.5, 1, 2, 5, 10, 20, 50 , 100, 200nM; the treatment concentration of paclitaxel was 0, 1, 2, 5, 10, 20, 50, 100, 200, 500nM; the treatment concentration of vinorelbine was 0, 5, 10, 20, 50, 100, 200, 500, 1000, 2000nM; Doxorubicin treatment concentration is 0, 20, 50, 100, 200, 500, 1000, 2000, 500...

Embodiment 2

[0046] To detect the cytotoxicity of ceritinib on SK-cbt-2, select a safe concentration without obvious cytotoxicity.

[0047] (1) Experimental method

[0048]SK-hep-1 and SK-cbt-2 were inoculated on 100mm culture dishes, cultivated for 72 hours, and removed the culture medium; digested with 0.25% trypsin, collected cells, counted cells, and prepared single cell suspensions with a concentration of 20,000 cells / ml, respectively Inoculate 0.2ml of single-cell suspension in each well into a 96-well plate, and the total number of cells in each well is 4000; after culturing overnight, add ceritinib (treatment concentrations are 0, 10, 20, 50, 100, 200, 500, 1000, 2000, 5000nM) were treated for 72h, the supernatant was removed, 0.2ml DMSO was added, and the OD value was detected with a microplate reader at a wavelength of 570nM.

[0049] (2) Experimental results

[0050] see results figure 1 , after 72 hours of 500nM ceritinib treatment, the viability of SK-hep-1 and SK-cbt-2 cel...

Embodiment 3

[0052] Ceritinib significantly enhanced the killing effect of docetaxel on SK-cbt-2 cells.

[0053] (1) Experimental method

[0054] SK-cbt-2 was inoculated on 100mm culture dishes, cultured for 72 hours, and the culture medium was removed; digested with 0.25% trypsin, collected cells, counted cells, prepared a single cell suspension with a concentration of 20,000 cells / ml, and inoculated 0.2ml single cells in each well. Add the cell suspension to columns 2-11 of a 96-well plate, and the total number of cells per well is 4000; culture overnight, without adding any reagents to column 2, and add 500nM ceretide to each well of cells in columns 3-11 At the same time, add 5, 10, 20, 50, 100, 200, 500, 1000, 2000nM) docetaxel in sequence, and treat them together for 72 hours, remove the supernatant, add 0.2ml DMSO, and detect the OD value with a microplate reader at a wavelength of 570nM .

[0055] (2) Experimental results

[0056] see results figure 2 , 500nM ceritinib combine...

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Abstract

The invention discloses an application of ceritinib in the preparation of a tumor chemotherapy drug sensitizer and an antitumor pharmaceutical composition. The antitumor pharmaceutical composition contains a chemotherapy drug and a sensitizer, wherein the sensitizer is ceritinib. Researches find that the ceritinib can be used as a tumor chemotherapy drug resistance sensitizer and can be combined with the chemotherapy drug in use, so that the drug resistance of tumors to the chemotherapy drug can be overcome, the treatment effect of the chemotherapy drug to drug-resistant tumor cells can be remarkably improved, and new ways and measures are provided for the effective treatment of the tumors.

Description

technical field [0001] The invention relates to the field of medicine, in particular to the application of ceritinib in the preparation of tumor chemotherapeutic drug sensitizers and an antitumor drug composition. Background technique [0002] Cancer is the number one "killer" that seriously threatens the life and health of our people, and has become a public health problem that needs to be solved urgently! The latest research shows that new cancer cases and deaths in my country are increasing year by year. Among them, there were about 4.292 million new cases of invasive cancer in 2015, with an average of about 12,000 new cases per day; at the same time, there were 2.814 million cancer deaths in 2015, with an average of about 12,000 new cases per day. 7,500 people died from cancer. [0003] At present, the main treatment methods for malignant tumors include surgery, radiotherapy and chemotherapy. For patients diagnosed with advanced tumors and patients with metastases, chem...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/506A61K45/06A61K31/337A61K31/475A61K31/704A61P35/00
CPCA61K31/337A61K31/475A61K31/506A61K31/704A61K45/06A61K2300/00
Inventor 蒋东海
Owner ZHEJIANG UNIV
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