Application of lactalbumin-oleic acid composite to preparation of medicines for restraining energy metabolism of tumor cells

A technology of oleic acid complex and lactalbumin, which is applied in the direction of antineoplastic drugs, drug combinations, peptide/protein components, etc., can solve problems that have not been evaluated, and achieve the effect of inhibiting energy metabolism

Inactive Publication Date: 2019-11-22
CHINA AGRI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the existing studies have not evaluated the changes in energy metabolism of tumor cells after treatment of tumor cells with α-LA-OA, and the mechanism of changes in energy metabolism of tumor cells caused by treatment of tumor cells with α-LA-OA

Method used

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  • Application of lactalbumin-oleic acid composite to preparation of medicines for restraining energy metabolism of tumor cells
  • Application of lactalbumin-oleic acid composite to preparation of medicines for restraining energy metabolism of tumor cells
  • Application of lactalbumin-oleic acid composite to preparation of medicines for restraining energy metabolism of tumor cells

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Embodiment 1——Preparation of α-LA-OA

[0039] The present embodiment provides the preparation method of lactalbumin-oleic acid complex (α-LA-OA), comprising the following steps:

[0040] Dissolve α-LA in phosphate buffer at pH 8.0 to make the final concentration of α-LA 1 mM, then add OA, wherein the molar ratio of α-LA and OA is 1:30, mix well and put in 45 ℃ constant temperature water bath shaker, react for 20 minutes; 4 ℃, 12000×g centrifugation for 15 minutes, then remove the OA not bound to the protein, store at 4 ℃ to obtain the α-LA-OA.

Embodiment 2

[0041] Example 2——Influence of α-LA-OA on Energy Metabolism of Xenograft Tumors in Nude Mice

[0042] Experimental animals: BALB / c nude mice, nonpregnant females, healthy and mature, 4-5 weeks old, SPF grade.

[0043] Establishment of tumor animal models:

[0044] After nude mice were adaptively fed for 5-7 days, liver cancer cells in the logarithmic growth phase were taken, digested with trypsin, and prepared into a cell suspension with PBS. The amount of cells inoculated in each nude mouse was 3×106, , subcutaneously injected into the head and tail of nude mice, each with an inoculation volume of 100-200 μL.

[0045] After inoculating the cells, observe the cell state every day until the tumor volume is 1cm 2 Drug treatment of mice was started at about 10 minutes. Phosphate Control was injected into the head tumor of each nude mouse, and α-LA-OA was injected into the tail tumor, 90 μL each time, 3 times a day for 7 consecutive days.

[0046] In order to study the effect ...

Embodiment 3

[0064] Example 3——Influence of α-LA-OA on Energy Metabolism of HepG2 Cells

[0065] Cell line: HepG2, human liver cancer cells, purchased from the Chinese Academy of Sciences Cell Bank, DMEM high glucose medium, 10% fetal bovine serum.

[0066] In this example, HepG2 cells were used as a model to explore the effects of α-LA-OA on tumor cell viability, glycolytic ATP production, and aerobic respiration ATP production in vitro, and to prove the effect of α-LA-OA on the energy metabolism of HepG2 cells. inhibition.

[0067] The effect of α-LA-OA action time on the energy metabolism of HepG2 cells: In order to study the effect of α-LA-OA on tumor cell activity, this example uses α-LA-OA with concentrations of 10, 20, 40, 60, and 80 μM After HepG2 cells were treated for 24 h, cell viability was detected by Cck-8 kit.

[0068] After HepG2 cells were treated with different concentrations of α-LA-OA and α-LA for 24 hours, the cell viability was as follows: Figure 6 shown. It can...

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Abstract

The invention discloses an application of a lactalbumin-oleic acid composite to preparation of medicines for restraining energy metabolism of tumor cells, and finds that alpha-LA-OA can resist the glycolysis process of tumor cells and reduce the consumption of oxygen by an aerobic respiration process of a mitochondrion and the generation amount of ATP. In addition, the invention further finds thatthe alpha-LA-OA can reduce generation of ATP in an HepG2 cell glucose metabolism way, so that the effect of restraining energy metabolism of tumor cells can be achieved; an HepG2 tumor cell model isused for confirming that the alpha-LA-OA can notably promote expression of mTORC2 target protein Rictor, mSin1 and Ser473-Akt, and the expression amount of various enzymes in the glycolysis way can benotably reduced. The alpha-LA-OA can activate an mTORC2 signal route, and can restrain activity of key enzymes in the glucose metabolism way, so as to reduce the energy metabolism for restraining tumor cells, by ATP.

Description

technical field [0001] The invention belongs to the field of biotechnology, and particularly relates to the application of lactalbumin-oleic acid complex (α-LA-OA) in the preparation of drugs for inhibiting energy metabolism of tumor cells. Background technique [0002] Cancer is a major public health problem worldwide. Although research on cancer prevention and treatment has progressed rapidly in recent years, its incidence remains high. According to reports, the global incidence of cancer increased by 28% from 2006 to 2016. Therefore, the development of new and effective anti-tumor drugs is still a research hotspot, and molecularly targeted drugs for tumor cells have received extensive attention. [0003] α-lactalbumin-oleic acid complex (α-LA-OA) has a good antitumor effect, and its selective killing of tumor cells without affecting the activity of healthy differentiated cells not only in human glioblastoma and bladder cancer Validated in a mouse model of , and in patie...

Claims

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Application Information

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IPC IPC(8): A61K38/38A61K47/54A61P35/00
CPCA61K38/38A61K47/542A61P35/00
Inventor 任发政杨志轩冷小京方冰李依璇
Owner CHINA AGRI UNIV
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