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Medicament for improving drug resistance of solid tumors against anti-vascular drugs and application of CPT1a inhibitor in medicament

An inhibitor and drug resistance technology, applied in antitumor drugs, drug combinations, medical preparations containing active ingredients, etc. effect of effect

Active Publication Date: 2019-09-13
义慧科技(深圳)有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, a major obstacle to antivascular therapy is that patients with malignancies often develop resistance to antivascular drugs, the mechanisms of which remain largely unknown

Method used

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  • Medicament for improving drug resistance of solid tumors against anti-vascular drugs and application of CPT1a inhibitor in medicament
  • Medicament for improving drug resistance of solid tumors against anti-vascular drugs and application of CPT1a inhibitor in medicament
  • Medicament for improving drug resistance of solid tumors against anti-vascular drugs and application of CPT1a inhibitor in medicament

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] Example 1: Co-treatment of tumors with antivascular drugs and CPT1a shRNA transfection vector in fat environment

[0067] Firstly, the CPT1a shRNA transfection vector was constructed: the Cpt1shRNA lentiviral particles transfected with Cpt1shRNA were used as the CPT1a shRNA transfection vector, which was purchased from Santa Cruz Biotechnology (California). The transduction process was performed according to the manufacturer's protocol provided by the company, and the CPT1a shRNA transfection vector can inhibit the expression of Cpt1 protein.

[0068] pair to about 1 x 10 5 MC38 and Hepa1-6 cells grown in a 12-well plate were grown at a density of 5×10 4 Cpt1shRNA transfection Cpt1shRNA lentiviral particle infection. Cells transduced with lentivirus were then selected with puromycin (2 μg / mL), and the knockdown efficiency of CPT1 was verified by standard quantitative real-time polymerase chain reaction (qPCR) method.

[0069] When constructing a specific CRC liver me...

Embodiment 2

[0074] Example 2: Co-treatment of tumors with antivascular drugs and CPT1a inhibitor drug carriers in fat environment

[0075] Constructing a CPT1a inhibitor drug carrier: the details are as follows: Etomoxir is dissolved in water to obtain a CPT1a inhibitor drug carrier solution.

[0076] When constructing the cell model, MC38 cells were seeded on a 96-well plate at a density of 2500 cells / well, and incubated in 100 μL of the above medium for 24 hours, and a hypoxic environment was provided to each well using a hypoxia kit ( Tumor cells will use free fatty acids in a hypoxic environment), and on the third day, each well was divided into the following groups: free fatty acids (FFA) and Etomoxir were not added (negative control group); only FFA was added; FFA and 50 μM Etomoxir were added ; FFA and 100 μM Etomoxir were added. Tumor cell growth in each well was assessed using the MTT assay system described above. Metabolism of tumor cells was determined using a hippocampal cel...

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Abstract

The invention provides a new application of a CPT1a inhibitor, in particular to an application of the CPT1a inhibitor in preparing a medicament for improving drug resistance of solid tumors against anti-vascular drugs. The CPT1a inhibitor acts on the CPT1a on the surface of the mitochondrial outer membrane of tumor cells, inhibits fatty acid from entering the mitochondrial matrix for oxidation, inhibits the uptake of the tumor cells on free fatty acid, recovers the sensitivity of the tumor cells against anti-vascular drug therapy, inhibits the proliferation of the tumor cells, promotes the apoptosis of the tumor cells, and can further achieve the effect of improving the drug resistance of solid tumors against the anti-vascular drugs. The invention also provides a medicament for improving drug resistance of the solid tumor against the anti-vascular drugs and a medicament for treating the solid tumor.

Description

technical field [0001] The invention relates to the technical field of medicines, in particular to a medicine for improving the resistance of solid tumors to antivascular medicines and the application of CPT1a inhibitors therein. Background technique [0002] Malignant tumors (such as solid tumors such as liver cancer, colon cancer, and breast cancer) have become the culprits that threaten human life, and the incidence rate is on the rise. Malignant tumor cells grow rapidly, metabolites accumulate, and tumor blood vessels are disordered. Clinically, antivascular drugs are usually used to treat patients with solid tumors, which can improve the survival time of patients to a certain extent. However, a major obstacle to antivascular therapy is that patients with malignancies often develop resistance to antivascular drugs, the mechanisms of which remain largely unknown. [0003] Therefore, it is necessary to provide a method that can improve the resistance of antivascular drugs...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K45/06A61P35/00
CPCA61K45/00A61K45/06A61P35/00
Inventor 杨云龙曹义海
Owner 义慧科技(深圳)有限公司
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