Synergistic drug compound for treating tumor and preparation method thereof

A drug complex, tumor technology, applied in antitumor drugs, drug combinations, pharmaceutical formulations, etc., can solve problems such as increasing the sensitivity of tumor cells, and achieve the effect of enhancing the therapeutic effect

Inactive Publication Date: 2016-08-24
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Studies have disclosed that the chemotherapy drug 5-FU and the monoclonal antibody drugs Trastuzumab (Trastuzumab) and Cetuximab (Cetuximab) can significantly induce cell autophagy and inhibit the autophagy of cells produced by these three drugs. Autophagy can significantly increase the sensitivity of tumor cells to treatment; so far, there have been no reports about human recombinant arginase inducing tumor cell autophagy and making compound drugs or compositions with autophagy inhibitors to treat tumors

Method used

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  • Synergistic drug compound for treating tumor and preparation method thereof
  • Synergistic drug compound for treating tumor and preparation method thereof
  • Synergistic drug compound for treating tumor and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Embodiment 1: Preparation of human recombinant arginase

[0037] The coding sequence of encoding human arginase was obtained by using the prior art PCR method. The coding sequence of the gene is 969bp in length, with enzyme cutting sites XhoI and EcoRI. Empty plasmid vector, connect the target gene to the vector and transform the ampicillin resistance plate, pick several positive transformants, take one of them to amplify and extract the plasmid, and carry out double digestion identification with XhoI and EcoRI endonuclease; extract the recombinant plasmid, The recombinant vector was digested with BglII to linearize it, and transformed into Pichia pastoris by electroporation; positive transformants were picked and screened on RDB, MM and MD plates to obtain clones with the phenotype his+muts, which were further carried out at the shaker level Induce expression, detect the expression of arginase on the shaker level by SDS-PAGE protein electrophoresis, thereby screening r...

Embodiment 2

[0039] Example 2: Formulating autophagy inhibitor drugs

[0040] (1) Preparation of chloroquine: Dissolve an appropriate amount of chloroquine in pure water to make a 10mmol / L storage solution, filter and sterilize with a 0.1 μm filter, store at 4°C, and dilute 500-1000 times for in vitro experiments to inhibit cell autophagy ;

[0041] (2) Preparation of ammonium chloride: Dissolve an appropriate amount of ammonium chloride in water to prepare a 0.4 mol / L storage solution, filter and sterilize with a 0.1 μm filter, and store at 4°C. In vitro experiments were diluted 50-80 times to inhibit cell autophagy;

[0042] (3) Preparation of hydroxychloroquine: Dissolve an appropriate amount of hydroxychloroquine in pure water to form a 10mmol / L stock solution, filter and sterilize with a 0.1 μm filter, store at 4°C, and dilute 500-1000 times in the in vitro laboratory for inhibition autophagy;

[0043] (4) Preparation of 3-MA: Take an appropriate amount of 3-MA dry powder to prepar...

Embodiment 3

[0047] Example 3: Human recombinant arginase induces autophagy in triple-negative breast cancer MDA-MB-231 cells

[0048] MDA-MB-231 cells were treated with 1U / ml arginase for 24h, then paraffin-embedded, sectioned, and stained, and the submicroscopic structure of the cells was observed under a transmission electron microscope. The results were as follows: figure 1 As shown in A, there are a large number of typical double-membrane structure autophagosomes in the cells of the administration group, but not found in the control group; treated with 1IU / ml arginase for 24h, and then Cyto-ID and Hoechst triple negative In breast cancer MDA-MB-231 cells, the green fluorescent spots were observed under the laser confocal microscope, and the results were as follows figure 1 B shows that there are a large number of fluorescent spots in the cells of the administration group, while the control group has fewer;

[0049] The collected triple-negative breast cancer MDA-MB-231 cells were was...

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Abstract

The invention belongs to the field of medicine and biotechnology, and relates to a synergistic drug compound for treating tumors and a preparation method thereof. The drug compound is composed of one or more cell autophagy inhibitors and arginase, especially human recombinant Arginase is made into a synergistic drug compound for treating tumors, and the synergistic drug compound can inhibit autophagy by inhibiting autophagy through autophagy inhibitors to increase tumor cells' ability to arginase. sensitivity, and enhance the therapeutic effect of arginase, especially human recombinant arginase, on tumors, especially triple-negative breast cancer cells. The drug compound of the present invention can be used for clinical treatment of breast cancer, melanoma, lung cancer, brain tumor, lymphoma, leukemia and myeloma.

Description

technical field [0001] The invention belongs to the fields of medicine and biotechnology, and relates to antitumor drugs, in particular to a synergistic drug compound for treating tumors and a preparation method thereof, in particular to a combination of one or more cell autophagy inhibitors and human recombinant arginine A synergistic drug compound made of acidase, the synergistic drug compound can be used to enhance the effect of human recombinant arginase on breast cancer, melanoma, lung cancer, brain tumor, breast cancer, Lymphoma, leukemia, and myeloma, especially triple-negative breast cancer. Background technique [0002] The prior art discloses that arginase is a key enzyme involved in the urea cycle in the liver of mammals, in which arginine is converted into ornithine and urea. Arginine is a semi-essential amino acid that maintains the growth of some tumor cells. When the level of arginine in tumor cells is lower than a certain value, it will lead to cell death. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K38/50A61P35/00A61P35/02
Inventor 鞠佃文王子玉李玉彬曾贤范佳君王绍飞宋平陈其成
Owner FUDAN UNIV
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