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Composition of autophagy inhibitor and lapatinib, and application thereof

An autophagy inhibitor, lapatinib technology, applied in the field of medicine, can solve problems such as undiscovered combination administration, and achieve the effect of enhancing the therapeutic effect

Inactive Publication Date: 2015-02-04
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] So far, there have been no reports about lapatinib-induced tumor cell autophagy and autophagy inhibitors and lapatinib made into compound drugs, compositions for combined administration or sequential administration

Method used

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  • Composition of autophagy inhibitor and lapatinib, and application thereof
  • Composition of autophagy inhibitor and lapatinib, and application thereof
  • Composition of autophagy inhibitor and lapatinib, and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1: Preparation of autophagy inhibitor drugs

[0038](1) Preparation of chloroquine: Dissolve an appropriate amount of chloroquine in pure water to make a 10mmol / L storage solution, filter and sterilize it with a 0.1μM filter, and store it at 4°C. Dilute 500-1000 times with PRMI-1640 medium for in vitro experiments. to inhibit autophagy;

[0039] (2) Prepare ammonium chloride: Dissolve an appropriate amount of ammonium chloride in water to make a 0.4mol / L storage solution, filter and sterilize with a 0.1μM filter and store at 4°C; dilute 50-80 times for in vitro experiments Inhibit autophagy;

[0040] (3) Preparation of hydroxychloroquine: Dissolve an appropriate amount of hydroxychloroquine in pure water to make a 10mmol / L storage solution, filter and sterilize with a 0.1μM filter, store at 4°C, dilute 500-1000 times in an in vitro laboratory to inhibit cells Autophagy;

[0041] (4) Preparation of 3-MA: Take an appropriate amount of 3-MA dry powder to prepa...

Embodiment 2

[0045] Example 2: Cell Culture

[0046] Breast cancer SKBR3 cells and gastric cancer N87 cells were cultured using PRMI-1640 medium containing 10% FBS and 1% penicillin-streptomycin; 5 The concentration of cells / mL was transferred to the cell culture plate for culture, and after 12 hours of culture, the cells in each group were given corresponding concentrations of lapatinib; for combined administration, 20 μM CQ or 2 mM 3-MA was added 1 hour before administration Inhibit the autophagy of SKBR3 and N87 cells; after continuous culture for 24 h, 48 h or 72 h, proceed to the next step.

Embodiment 3

[0047] Example 3: Lapatinib can inhibit the proliferation of SKBR3 and N87 cells

[0048] Plant SKBR3 and N87 cells of appropriate concentration in a 96-well culture plate, add lapatinib to make the final concentration of lapatinib 0-1.6 μM, culture for 48 h, add 10 μL MTT solution to each well, and place in the incubator Leave it for 4 h, then dissolve it with DMSO solution, measure the optical density value (O.D.) at 570nm, the result is as follows figure 1 As shown in A and B, lapatinib has good efficacy on SKBR3 and N87 cells and lapatinib has a good dose-dependent killing effect on SKBR3 and N87 cells.

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PUM

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Abstract

The invention belongs to the technical field of medicines, and relates to a medicine composition of autophagy inhibitor and lapatinib, and an application thereof. The medicine composition comprises a cell autophagy inhibitor and lapatinib, wherein the cell autophagy inhibitor is one or more selected from 3-MA, wortmannin, LY294002, cycloheximide, bafilomycin A1, NH4Cl, chloroquine and hydroxychloroquine. The medicine composition can inhibit lapatinib-induced tumor cell autophagy, offset an antagonistic effect of tumor for lapatinib caused by cell autophagy and significantly enhance a curative effect of lapatinib on the tumor. The medicine composition provided by the invention can enhance a killing effect of lapatinib on the tumor, enhance the curative effect of lapatinib, and can be used for treating malignant tumor.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a new pharmaceutical composition for treating tumors; in particular, it relates to a pharmaceutical composition of an autophagy inhibitor and lapatinib and its application; the pharmaceutical composition is used for treating tumors. Background technique [0002] In recent years, with the rapid development of tumor molecular targeted therapy, molecular targeted therapy drugs emerge in an endless stream; usually, molecular targeted therapy drugs can be divided into two types: macromolecular monoclonal antibodies (monoclonal antibodies) and small molecule compounds according to the molecular size of the drug; Among them, the monoclonal antibody recognizes the extracellular distinguishable region of the receptor, competes with growth factors for binding to the receptor, and inhibits the activation of the signal transduction system, thereby inhibiting the proliferation and spread of can...

Claims

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Application Information

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IPC IPC(8): A61K31/52A61K31/585A61K31/5377A61K31/517A61K33/02A61P35/00A61P35/02A61K31/45A61K31/365A61K31/4706
CPCA61K31/365A61K31/45A61K31/4706A61K31/517A61K31/52A61K31/5377A61K31/585A61K33/02A61K2300/00
Inventor 鞠佃文王晓丹王子玉曾贤李玉彬范佳君王绍飞
Owner FUDAN UNIV
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