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Enhancers of antitumor activity of chemotherapeutic agents

一种化学治疗剂、治疗剂的技术，应用在制或治疗含领域，能够解决尚未阐明支链氨基酸分化的影响等问题，达到预防转移和复发的效果

Inactive Publication Date: 2016-04-27
EA PHARMA CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Nonetheless, the effect of branched-chain amino acids on the differentiation of cancer stem cells into cancer non-stem cells has not been elucidated so far

Method used

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  • Enhancers of antitumor activity of chemotherapeutic agents
  • Enhancers of antitumor activity of chemotherapeutic agents
  • Enhancers of antitumor activity of chemotherapeutic agents

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0106] An embodiment, which contains only isoleucine or its salt as a branched chain amino acid;

[0107] An embodiment, which contains only leucine or its salt as a branched chain amino acid;

[0108] An embodiment, which contains only valine or its salt as a branched chain amino acid;

[0109] An embodiment, which contains isoleucine or its salt and leucine or its salt as branched chain amino acids;

[0110] An embodiment, which contains isoleucine or its salt and valine or its salt as branched chain amino acids;

[0111] An embodiment, which contains leucine or its salt and valine or its salt as branched chain amino acids; and

[0112] One embodiment contains isoleucine or its salt, leucine or its salt, and valine or its salt as branched chain amino acids.

[0113] The agent or composition of the present invention preferably contains isoleucine or its salt, leucine or its salt, and valine or its salt.

[0114] To the extent that the agent of the present invention has the desired activit...

Embodiment 1

[0171] Example 1: The effect of BCAA on the expression of stem cell markers and differentiation markers in human liver cancer cell line HAK4

[0172] At a concentration of 12000 cells / well, human hepatoma cell line HAK4 cells were plated and cultured in 2mMBCAA or LC2.5% medium for 72 hours. BCAA is a mixture of isoleucine, leucine and valine (weight ratio: isoleucine:leucine:valine=1:2:1.2). The concentration of BCAA "2mM" is the total concentration of all amino acids of isoleucine, leucine and valine.

[0173] The composition of the LC2.5% medium is shown in the table below. It should be noted that the "2.5%" in LC2.5% is the bovine serum content.

[0174] Table 1

[0175]

Composition (nmol / ml) Glycine280 L-Alanine307 L-serine151 L-threonine138 L-cystine 2HCl67 L-methionine75 L-glutamine689 L-Asparagine64 L-glutamic acid53 L-Aspartic Acid4 L-valine175 L-Leucine100 L-Isoleucine53 L-phenylalanine99 L-tyrosine133 L-tryptophan45 L-Lysine-HCl184 L-Arginine-HCl92...

Embodiment 2

[0187] Example 2: The effect of the combined use of 5-FU (5-fluorouracil) and BCAA on human liver cancer cell line HAK4 (in vitro test)

[0188] At a concentration of 3000 cells / well, the human hepatoma cell line HAK4 cells were plated and cultured for 72 hours under the following conditions:

[0189] ?LC2.5% medium

[0190] ?BCAA(2mM)

[0191] ?5-FU(2.5μg / ml)

[0192] ?BCAA(2mM)+5-FU(2.5μg / ml).

[0193] After 72 hours, using ApoAlert Annexin V-FITC Apoptosis Kit (Clontech), cells were stained with Annexin V and fixed, and apoptotic cells (%) were detected by ArrayScan (ThermoFisher).

[0194] Specifically, wash the cells in a 96-well plate with 1X binding buffer, add 40μl of 1X binding buffer containing Annexin V (1μl) to each well, and incubate the cells in the dark at room temperature for 5-15 min . The cells were washed and fixed with 2% formaldehyde. 100μl of PBS containing Hoechst33258 solution was added, and the cells were incubated in the dark for 5 minutes, and the apoptotic ...

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Abstract

The present invention relates to an agent for enhancing the antitumor activity of a chemotherapeutic agent for cancer containing cancer stem cells, the agent containing at least one branched-chain amino acid selected from isoleucine, leucine, and valine or a salt thereof . The present invention also relates to an agent for treating cancer containing cancer stem cells, the agent comprising at least one branched-chain amino acid selected from isoleucine, leucine, and valine or a salt thereof and a chemotherapeutic agent combination. The present invention also relates to an agent for preventing metastasis or recurrence of cancer containing cancer stem cells, which agent contains at least one branched-chain amino acid or a salt thereof selected from isoleucine, leucine and valine and Combinations of Chemotherapeutic Agents.

Description

Technical field [0001] The present invention relates to an agent containing branched chain amino acids for enhancing the antitumor activity of chemotherapeutic agents against cancers containing cancer stem cells, an agent containing branched chain amino acids, and an agent containing branched chain amino acids for inducing the differentiation of cancer stem cells, and Agents containing a combination of branched chain amino acids and chemotherapeutic agents, etc., used to inhibit or treat the metastasis or recurrence of cancers containing cancer stem cells. Background technique [0002] Cancer stem cells are one of the subgroups of cancer cells contained in tumors, have self-replication ability and pluripotency, and have the ability to cause cancer when they metastasize orthotopically (Non-Patent Document 1). [0003] In different cancers, the existence of markers specifically expressed in cancer stem cells is known, and based on the expression of such markers, it is possible to eva...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/198A23L33/175A61K31/513A61K45/00A61P1/00A61P1/16A61P35/00A61P43/00
CPCA23V2002/00A61K31/513A61K45/06A23L33/175A61K31/198A61P1/00A61P1/16A61P35/00A61P35/04A61P43/00A61K2300/00A23V2200/308A61K31/4412A61K31/53
Inventor 西谷忍矢野博久
Owner EA PHARMA CO LTD
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