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Application of cyclic dinucleotide cgamp in anti-liver metastasis of colorectal cancer

A technology for colorectal cancer and liver metastases, applied in the field of biomedicine, can solve the problem that liver metastases cannot be radically removed, etc.

Active Publication Date: 2019-12-03
HANGZHOU XINGAO BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

About 50% to 60% of patients with colorectal cancer develop liver metastases at the time of diagnosis or after radical surgery, and the vast majority of patients (80% to 90%) cannot obtain radical resection of liver metastases

Method used

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  • Application of cyclic dinucleotide cgamp in anti-liver metastasis of colorectal cancer
  • Application of cyclic dinucleotide cgamp in anti-liver metastasis of colorectal cancer
  • Application of cyclic dinucleotide cgamp in anti-liver metastasis of colorectal cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0011] Embodiment 1: Preparation of cGAMP

[0012] cGAMP (cyclized-GMP-AMP) is catalyzed and synthesized by cyclized cGMP-AMP dinucleotide synthetase (cGAS) under activation conditions after binding to DNA according to literature method. The purity is above 98%. (Pingwei Li, et al., Immunity, 2013, 39(6), 1019-1031.)

Embodiment 2

[0013] Example 2: Anti-tumor effect of cGAMP (cyclized-GMP-AMP) The tumor-bearing mouse model was used to detect the inhibitory effect of cGAMP on liver metastasis of colorectal cancer in animals.

[0014] Test drug

[0015] Name: cGAMP

[0016] Appearance: white powder

[0017] Vehicle: normal saline.

[0018] Preparation method: Prepare the solution with the required concentration with physiological saline solution before use.

[0019] Test drug concentration: 1mg / ml, 2mg / ml.

[0020] animal

[0021] Species, strains, gender, body weight, source, certificate of conformity

[0022] C57 mice, male, weighing 16-18 g, 6-8 weeks old, were purchased from Shanghai Slack Experimental Animal Co., Ltd. [Experimental animal quality certificate number: SCXK (Shanghai) 2007-0005].

[0023] Feeding conditions

[0024] All mice were free to forage for food and drink water, and were kept at room temperature (23±2)°C in the Experimental Animal Center of a Military Medical University o...

Embodiment 3

[0049] Embodiment 3: Activation efficiency of mouse dendritic cells (DC cells) tested by flow cytometry

[0050] See Example 2 for mouse breeding and colorectal cancer metastasis model modeling. Anti-CD40, CD80, CD86, MHC II, isotype control antibodies and other flow antibodies were purchased from eBiosciences, CD11c+ antibody magnetic beads were purchased from MiltenyiBiotech, and flow cytometers were purchased from BD. The mice were killed 14 days after the administration, and the spleens of the mice were taken, ground and crushed, and the cells were filtered through a 40 μm pore membrane. Centrifuge at 1000rpm for 10 minutes to separate the immune cells in the spleen, lyse the erythrocytes with erythrocyte lysate until the erythrocytes are completely dissolved, and then centrifuge at 1000rpm for 10 minutes to separate the unlysed immune cells. Separate DC cells with CD11c+ antibody magnetic beads, add anti-CD40, CD80, CD86, MHC II FAC antibodies (diluted with FACS buffer) ...

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Abstract

The invention belongs to the technical field of medicine, and particularly discloses application of cGAMP in treatment of colorectal cancer hepatic metastases. Studies show that cGAMP can remarkably inhibit colorectal cancer from metastasizing to the liver, has an obvious antineoplastic function, and can be utilized for preparing anti-tumor metastasis medicine. A C57BL / 6 mouse colorectal cancer metastasis mold proves that cGAMP has a remarkable inhibition function on colorectal cancer cell strains MC38, tumor cells are prevented from metastasizing to the liver, and dendritic cells (DC cells) are activated, IL-2, IFN-gamma and IFN-beta expression relevant to immune response is improved, so that cGAMP can be utilized for treating colorectal cancer hepatic metastases.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to the application of a cyclic dinucleotide (cGAMP) in anti-colorectal cancer liver metastasis and in the preparation of anti-colorectal cancer liver metastasis medicine. Background technique [0002] Colorectal cancer, also known as colorectal cancer, rectal cancer, or bowel cancer, is a cancer originating from the colon or rectum, and is a common malignant tumor in the gastrointestinal tract. Due to the abnormal growth of cells, it can invade or spread to other parts of the body. Early symptoms include blood in the stool, changes in bowel habits, weight loss, and a feeling of tiredness. Most colorectal cancers are caused by poor living habits and tissue aging, while a few are genetic diseases. Risk factors include diet, obesity, smoking, and lack of physical activity. Diets that increase cancer risk include red or processed meat, and alcohol, among others. Other...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/7084A61P35/00A61P35/04
Inventor 张跃茹袁红程浩谭瀛轩
Owner HANGZHOU XINGAO BIOTECH CO LTD
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