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Application of shikonin compounds in the preparation of drugs promoting trail anti-tumor activity

A technology of anti-tumor activity and shikonin, which is applied in anti-tumor drugs, drug combinations, organic active ingredients, etc., and can solve problems such as TRAIL restrictions

Active Publication Date: 2022-03-11
EXPERIMENTAL RES CENT CHINA ACAD OF CHINESE MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, during the actual application of TRAIL, some tumors were found to be resistant to it; at the same time, some tumors that were originally sensitive to it may also develop acquired resistance after long-term TRAIL treatment
These reasons make TRAIL limited in actual clinical application

Method used

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  • Application of shikonin compounds in the preparation of drugs promoting trail anti-tumor activity
  • Application of shikonin compounds in the preparation of drugs promoting trail anti-tumor activity
  • Application of shikonin compounds in the preparation of drugs promoting trail anti-tumor activity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0069] Example 1, SKN enhances the anti-tumor activity of TRAIL

[0070] GA (Glycyrrhizic Acid, glycyrrhizic acid) is a product of Shanghai Ziyuanye Biotechnology Co., Ltd., SKN (shikonin) is a product of Sigma Company, and TRAIL is derived from humans. Its amino acid sequence is as follows: NCBI Reference Sequence: NP_003801.1 (06-MAY -2017), consisting of 281 amino acid residues, is a product of Peprotech.

[0071] TRAIL resistant human lung adenocarcinoma cell A549, human cervical cancer cell HeLa, human pancreatic cancer cell PANC1, TRAIL sensitive cell human colon cancer cell Colo205, human colorectal cancer cell HCT116, and normal cell line human embryonic kidney cell HEK-293 Cultured with RPMI1640 medium and DMEM medium.

[0072] The above-screened GA, SKN and TRAIL were combined to detect whether they could promote TRAIL to kill tumor cells. The specific experiment is as follows:

[0073] 1.1 Determination of TRAIL dosage

[0074] TRAIL resistant cells human lung a...

Embodiment 2

[0091] Example 2. Research on the mechanism of synergistic induction of apoptosis by SKN and TRAIL

[0092] 1.1 Western blot detection of intracellular apoptosis-related proteins

[0093] After the above cell viability CCK8 detection and Annexin V-PI double staining flow cytometry verification, it was shown that the combination of SKN and TRAIL significantly increased the killing of TRAIL on its resistant cell lines A549 and PANC1 mainly through apoptosis. In order to further explore whether the combination of the two is caused by the exogenous apoptotic pathway mediated by cell surface death receptors, or induced by the endogenous mitochondrial apoptotic pathway, the active enzymes related to the exogenous pathway were investigated by Western blot method was tested.

[0094] For SKN, TRAIL, TRAIL and SKN combined drug group and blank group, Western blot was used to detect apoptosis-related proteins: Caspase3, Caspase8, Caspase9, pro-apoptotic protein: Bax, anti-apoptotic pro...

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Abstract

The invention discloses the application of shikonin compounds in the preparation of drugs for promoting the anti-tumor activity of TRAIL. The invention provides the application of shikonin compounds in the preparation of drugs for enhancing the anti-tumor activity of A, and the A is TRAIL recombinant protein or TRAIL modification. Experiments have shown that adding low-dose TRAIL co-stimulation after SKN pretreatment can significantly increase the killing effect of TRAIL on A549, HeLa, PANC1 and HCT116, and has no cytotoxic effect on the normal cell line HEK‑293. It shows that the shikonin compounds can be used to enhance the anti-tumor activity of TRAIL, TRAIL recombinant protein or TRAIL modification.

Description

technical field [0001] The invention relates to the application of shikonin compounds in the preparation of anti-tumor activity-promoting drugs in the field of anti-tumor. Background technique [0002] Shikonadhiquinone compounds are a class of main bioactive components of comfrey, which have multiple functions such as antibacterial, anti-inflammatory, and anti-cancer, and are used as natural pigments in medicine, cosmetics, and printing and dyeing industries. The core of the naphthoquinone compounds contained in comfrey is mostly 5,8-dihydroxynaphthoquinone, which has an isohexene side chain, and the R-type shikonaquinone (shikonin) is the 5th position of the isohexene side chain The substituent spatial configuration of is R configuration. At present, 15 kinds of shikonin compounds have been isolated from Shikonin, and the structure core of shikonin compounds is shown in formula 1: [0003] [0004] The substituent groups of shikonin compounds are different, such as me...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/122A61P35/00A61K38/17A61K9/51A61K9/16
CPCA61K38/177A61K31/122A61K9/1641A61K9/5169A61K2300/00
Inventor 刘长振郭志兰李晶哲
Owner EXPERIMENTAL RES CENT CHINA ACAD OF CHINESE MEDICAL SCI
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