Application of combination of bortezomib and panobinostat or vorinostat in preparing drugs for treating drug-resistant MLL

A technology of bortezomib and panobinostat, which is applied in the field of biomedicine to solve the problem of drug resistance, effectively treat and improve the effect of treatment

Active Publication Date: 2019-10-11
RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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[0010] However, there are currently no effec

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  • Application of combination of bortezomib and panobinostat or vorinostat in preparing drugs for treating drug-resistant MLL
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  • Application of combination of bortezomib and panobinostat or vorinostat in preparing drugs for treating drug-resistant MLL

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Embodiment 1

[0034] 1 Materials and methods

[0035] The following cell lines were used in this study: B-cell leukemia cell line RS4 with MLL ectopic rearrangement; 11 and SEM were purchased from Deutsche Sammlung von Mikroorganismen und Zellkulturen (DMSZ). All suspension cell lines were cultured with RPMI 1640 medium containing 10% fetal bovine serum, placed at 37°C, 5% CO 2 , 95% air humidity incubator culture. The cells were replaced every other day, and the cell concentration was adjusted to 5×10 5 / ml and 2×10 6 Between pieces / ml. Proteasome inhibitor bortezomib resistant cells were obtained from parental cells treated with increasing concentrations of bortezomib for at least four weeks. The specific drug concentration is the half maximal inhibitory concentration (IC) of the drug corresponding to the parental cells. 50 ), that is, adding 5 nM bortezomib, changing the medium every three days and adding new drugs to continue the treatment for four weeks. During drug treatment, mo...

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Abstract

The invention relates to application of a combination of bortezomib and panobinostat or vorinostat in preparing drugs for treating drug-resistant MLL. It is proved that panobinostat and vorinostat canrestore the sensitivity of MLL drug-resistant cells, reverse the bortezomib drug resistance in the body of a mouse, reduce the production of drug-resistant cells and prolong the lifetime. Through theapplication, solving of the drug resistance problem of MLL is facilitated, and the treatment effect on malignant tumors of this type in the personalized medical treatment era is further improved.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to the application of the composition of bortezomib and panobinostat or vorinostat in the preparation of drugs for treating drug-resistant MLL leukemia. Background technique [0002] Proteasome inhibitors (proteasome inhibitor, PI) can effectively induce tumor cell apoptosis, since the late 1990s, clinical trials have been carried out on a variety of malignant tumors. Currently, three proteasome inhibitors (bortezomib, carfilzomib, and ixazomib) have been approved by the U.S. Food and Drug Administration (FDA) for clinical treatment of multiple myeloma. , MM) and mantle-cell lymphoma (mantle-cell lymphoma, MCL). [0003] Bortezomib (trade name valcade, Wanke) is the first proteasome inhibitor approved for clinical use. Bortezomib binds to the catalytic site of the 26S proteasome, thereby inhibiting the proteolytic activity of the β5, β2 and β1 subunits. Initially approved for...

Claims

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Application Information

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IPC IPC(8): A61K38/05A61P35/02A61K31/4045A61K31/16
CPCA61K38/05A61K31/4045A61K31/16A61P35/02A61K2300/00Y02A50/30
Inventor 刘晗葛茂林李丹乔智孙燕
Owner RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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