CN110269864A - Application of the Inokopolyose in anti-colorectal carcinoma - Google Patents
Application of the Inokopolyose in anti-colorectal carcinoma Download PDFInfo
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- CN110269864A CN110269864A CN201810211374.6A CN201810211374A CN110269864A CN 110269864 A CN110269864 A CN 110269864A CN 201810211374 A CN201810211374 A CN 201810211374A CN 110269864 A CN110269864 A CN 110269864A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Abstract
The application that the present invention relates to Inokopolyoses in anti-colorectal carcinoma.Specifically, Inokopolyose, which can be used for preparing, is selected from the group the promotor of cell factor: Bmp3, Csf2, Ifnb1, Il15, Il17c, Il17f, Il2, Il23a, Il5, Inhba, Adipoq, Csf3, Il10, Il24, Il6, Inha, or combinations thereof.Inokopolyose can be also used for preparation and be selected from the group the inhibitor of cell factor: Cd40lg, Il10, Il13, Il16, Il1b, Lta, Ltb, Tnf, Tnfsf8, Il23a, Spp1, or combinations thereof.Inokopolyose can treat and/or pre- preventing tumor in mouse colorectal cancer model；Inokopolyose seems there is slight immunostimulation in normal mouse；Inokopolyose may be by the generation by inhibiting IL23 and enteritis in the tumor prevention effect of colorectal cancer model mice.
Description
Technical field
The present invention relates to the application of field of biotechnology more particularly to Inokopolyose in anti-colorectal carcinoma.
Background technique
Inokopolyose (Achyranthes bidentata polysaccharides, ABPS) is in Achyranthes bidentata Bl root
Bioactive polysaccharide.Experiment and clinical research show that there is enhancing tumor patient to exempt to tolerance, the adjusting of antineoplaston for it
The pharmacological functions such as epidemic disease, anti-aging, hypoglycemic and dredging collateral and promoting blood circulation.ABPS uniform component, by fructose: glucose (8:1) forms,
Molecular weight is 1400D, and its chemical structure is accredited out.It has been reported that ABPS stimulation DC can cooperate with CIK to improve
To the killing activity of Human colorectal cancer cells strain SW480.But mechanism of action of the ABPS in anti-colorectal carcinoma is also indefinite.
Therefore, this field needs purposes of the research Inokopolyose in anti-colorectal carcinoma.
Summary of the invention
The application that the object of the present invention is to provide Inokopolyoses in anti-colorectal carcinoma.
The first aspect of the present invention provides a kind of purposes of Inokopolyose, is used to prepare the promotor of cell factor, or
It is used to prepare a preparation or composition, the preparation or composition are used to promoting or raising the cytokine-expressing in cell,
Wherein, the cell factor is selected from the group: Bmp3, Csf2, Ifnb1, Il15, Il17c, Il17f, Il2,
Il23a, Il5, Inhba, Adipoq, Csf3, Il10, Il24, Il6, Inha, or combinations thereof.
In another preferred example, the cell factor comes from mammal.
In another preferred example, the mammal includes people and non-human mammal, is preferably comprised rodent (such as
Mouse, rat), Primate (such as people).
In another preferred example, the promotor includes the expression for promoting the cell factor, or improve the cell because
The expression quantity of son.
In another preferred example, the promotor include promote the expression quantity of the cell factor be enhanced about more than once (with
Control is compared).
In another preferred example, the cell factor comes from enterocyte.
In another preferred example, the enterocyte include: colon cell, rectal cell, or combinations thereof.
In another preferred example, the cell factor comes from normal cell or cancer cell, preferably, thin from Normal Colon
Born of the same parents, normal rectal cell, colorectal cancer cell, or combinations thereof.
In another preferred example, the cell includes normal cell；And/or
The cell factor is selected from the group: Bmp3, Csf2, Ifnb1, Il15, Il17c, Il17f, Il2, Il23a, Il5,
Inhba, or combinations thereof.
In another preferred example, the promotor of the cell factor from normal cell, the cell factor choosing are used to prepare
From the following group: Bmp3, Il17c, Il17f, Il23a, Il5, or combinations thereof.
In another preferred example, the normal cell be normal colon cell, normal rectal cell, or combinations thereof.
In another preferred example, the cell includes cancer cell；And/or
The cell factor is selected from the group: Adipoq, Csf3, Il10, Il24, Il5, Il6, Inha, or combinations thereof.
In another preferred example, it is used to prepare the promotor of the cell factor from cancer cell, the cell factor is selected from
The following group: Adipoq, Csf3, Il5, Il6, or combinations thereof.
In another preferred example, the cancer cell is colorectal cancer cell.
The second aspect of the present invention provides a kind of purposes of Inokopolyose, is used to prepare the inhibitor of cell factor, or
It is used to prepare a preparation or composition, the preparation or composition are used to inhibiting or lowering the cytokine-expressing in cell,
Wherein, the cell factor is selected from the group: Cd40lg, Il10, Il13, Il16, Il1b, Lta, Ltb, Tnf,
Tnfsf8, Il23a, Spp1, or combinations thereof.
In another preferred example, the inhibitor includes the expression for inhibiting the cell factor, or reduce the cell because
The expression quantity of son.
In another preferred example, the inhibitor include inhibit the expression quantity of the cell factor reduce by one times or more (with
Control is compared).
In another preferred example, the cell factor comes from mammal.
In another preferred example, the mammal includes people and non-human mammal, is preferably comprised rodent (such as
Mouse, rat), Primate (such as people).
In another preferred example, the cell factor comes from enterocyte.
In another preferred example, the enterocyte include: colon cell, rectal cell, or combinations thereof.
In another preferred example, the cell factor comes from normal cell or cancer cell, preferably, thin from Normal Colon
Born of the same parents, normal rectal cell, colorectal cancer cell, or combinations thereof.
In another preferred example, the cell includes normal cell；And/or
The cell factor is selected from the group: Cd40lg, Il10, Il13, Il16, Il1b, Lta, Ltb, Tnf, Tnfsf8 or
A combination thereof.
In another preferred example, the inhibitor of the cell factor from normal cell, the cell factor choosing are used to prepare
From the following group: Cd40lg, Il16, Il1b, Ltb, Tnf, or combinations thereof.
In another preferred example, the normal cell be normal colon cell, normal rectal cell, or combinations thereof.
In another preferred example, the cell includes cancer cell；And/or
The cell factor is selected from the group: Il13, Il23a, Spp1, or combinations thereof.
In another preferred example, the cancer cell is colorectal cancer cell.
The third aspect of the present invention provides a kind of purposes of Inokopolyose, is used to prepare prevention and/or treating cancer
Pharmaceutical composition or preparation.
In another preferred example, the cancer is colorectal cancer, preferably inflammatory colorectal cancer.
It should be understood that above-mentioned each technical characteristic of the invention and having in below (eg embodiment) within the scope of the present invention
It can be combined with each other between each technical characteristic of body description, to form a new or preferred technical solution.As space is limited, exist
This no longer tires out one by one states.
Detailed description of the invention
Fig. 1 shows the influence that ABPS composes cell factor in mouse Colon and rectum.Figure A: C57BL/6 mouse is divided into two
Group, every group 10.One group is experimental group, carries out ABPS stomach-filling processing, dosage 200mg/kg by time point as shown in the figure.It is another
Group is control group, carries out sterile water stomach-filling processing by time point as shown in the figure.Figure B and figure C: mouse Colon and rectum is taken, is then extracted
Total serum IgE, reverse transcription carry out the expression that PCR Array detects 84 kinds of mouse cytokines at cDNA, wherein with control group group
Middle Cytokine Expression Level is knitted as control, 84 kinds of cytokine up regulation or downward situation thermal map analysis (figure B) and its tool
Body raises multiple (figure C).
Fig. 2 shows ABPS to the prevention effect and possible mechanism of action for inducing mouse colorectal cancer.Wherein, scheme A: will
C57BL/6 mouse is divided into two groups, and every group 10, and use oxidized azoethane/dextran sulfate sodium (AOM/DSS) inducing mouse
Inflammation associated colorectal cancer model, during which carry out stomach-filling processing: experimental group is handled by the stomach-filling of 200mg/kg Inokopolyose, control
Group carries out stomach-filling processing with sterile water.Scheme colorectal cancer tumor formation number in B:ABPS stomach-filling processing group and is far less than control group.Scheme C
With figure D: detecting the expression of 84 kinds of mouse cytokines, 84 kinds of cytokine up regulation or downward using PCR Array method
Situation thermal map analyzes (figure C) and it particularly adjusts multiple (figure D).
Specific embodiment
The present inventor after extensive and in-depth study, for the first time it was unexpectedly observed that Inokopolyose can be used for prepare be selected from
The promotor of the following group cell factor: Bmp3, Csf2, Ifnb1, Il15, Il17c, Il17f, Il2, Il23a, Il5, Inhba,
Adipoq, Csf3, Il10, Il24, Il6, Inha, or combinations thereof.Inokopolyose can be also used for preparation be selected from the group cell because
Son inhibitor: Cd40lg, Il10, Il13, Il16, Il1b, Lta, Ltb, Tnf, Tnfsf8, Il23a, Spp1, or combinations thereof.
The present invention has detected the influence that Inokopolyose composes cell factor in normal mouse Colon and rectum, then inflammation associated using mouse
Colorectal cancer model detects the activity and its mechanism of action of ABPS anti-colorectal carcinoma.Inokopolyose in mouse colorectal cancer model,
It can treat and/or pre- preventing tumor；Inokopolyose seems there is slight immunostimulation in normal mouse；Inokopolyose is straight in knot
The tumor prevention effect of intestinal cancer model mice may be by the generation by inhibiting IL23 and enteritis.On this basis, it completes
The present invention.
Term
Unless otherwise defined, otherwise whole technologies used herein and scientific term all have such as fields of the present invention
The normally understood identical meanings of those of ordinary skill.
Inokopolyose (Achyranthes bidentata polysaccharides, ABPS) is in Achyranthes bidentata Bl root
Bioactive polysaccharide.Experiment and clinical research show that there is enhancing tumor patient to exempt to tolerance, the adjusting of antineoplaston for it
The pharmacological functions such as epidemic disease, anti-aging, hypoglycemic and dredging collateral and promoting blood circulation.ABPS uniform component, by fructose: glucose (8:1) forms,
Molecular weight is 1400D, and its chemical structure is accredited out.
Advantages of the present invention specifically includes that
1. present invention discover that Inokopolyose can prevent and/or treat tumour, and it was found that the oncotherapy of Inokopolyose
Prevention effect may be by the generation by inhibiting IL23 and enteritis.
2. present invention discover that Inokopolyose has slight immunostimulation to normal cell.
3. present invention firstly discovers that Inokopolyose, which can be used for preparing, is selected from the group the promotor of cell factor: Bmp3,
Csf2、Ifnb1、Il15、Il17c、Il17f、Il2、Il23a、Il5、Inhba、Adipoq、Csf3、Il10、Il24、Il6、
Inha, or combinations thereof；Can be also used for preparation and be selected from the group the inhibitor of cell factor: Cd40lg, Il10, Il13, Il16,
Il1b, Lta, Ltb, Tnf, Tnfsf8, Il23a, Spp1, or combinations thereof.Therefore, the present invention is that exploitation Inokopolyose is straight in resistive connection
Novel drugs in intestinal cancer are laid a good foundation, and are extremely had use value.
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention
Rather than it limits the scope of the invention.In the following examples, the experimental methods for specific conditions are not specified, usually according to conventional strip
Part, such as Sambrook et al., molecular cloning: laboratory manual (New York:Cold Spring Harbor
Laboratory Press, 1989) condition described in, or according to the normal condition proposed by manufacturer.Unless otherwise stated, no
Then percentage and number are weight percent and parts by weight.
Experimental method:
1.1 ABPS handle C57BL/6 mouse
ABPS dry powder is dissolved in sterile water and is made into appropriate concentration, intragastric administration on mice administration is then carried out with 200mg/kg dosage,
Stomach-filling is primary every other week, and stomach-filling 12 times, then carries out correlation analysis altogether.
The inflammation associated colorectal cancer model of mouse of 1.2 oxidized azoethanes/dextran sulfate sodium (AOM/DSS) induction
Building
Every group of 6-8 week old C57BL/6 male mice each 10 are ordered, SPF grades of animal houses is put in and is raised to weight 25g
Then left and right carries out animal model induction.First at mouse peritoneal for the first time injection carcinogen oxidized azoethane (AOM)
Reason, after a week second of intraperitoneal injection AOM processing again.After a week, mouse drinking water changes the drinking water containing DSS into, holds for AOM processing
It is continuous to drink one week, it then changes that normal drinking water is for 2 weeks, and then alternately DSS is handled three times again with this into, mouse inflammation can be obtained
Property colorectal cancer model.
1.3 PCR Array analyze the expression of 84 cell factors
The normal colorectal carcinoma of appropriate mouse or the inflammation associated colorectal cancer tumor tissues of mouse are taken, Trizol method is utilized
Total serum IgE is extracted, then using Reverse Transcriptase kit (Takara, Japan) the first chain cDNA of synthesis, is examined for following PCR Array
It surveys.Use the RT of triumphant outstanding person2ProfilerTMPCR Array Mouse Common Cytokines analyzes related 84 genes
Expression carries out PCR analysis using ABI ViiA7 standard PCR system.
The influence that 1 ABPS of embodiment composes cell factor in mouse Colon and rectum
C57BL/6 mouse is selected in influence for Systematic Analysis ABPS to cytokine-expressing in Colon and rectum, this experiment
Carry out continuous 3 months stomach-filling ABPS processing.C57BL/6 mouse is divided into two groups, every group 10.One group is experimental group, by as schemed
Time point shown in 1A carries out ABPS stomach-filling processing, dosage 200mg/kg.Another group is control group, by time point as shown in Figure 1A
Carry out sterile water stomach-filling processing.Then remove Colon and rectum, extract total serum IgE and reverse transcription at cDNA carry out PCR Array analysis (see
Experimental method).The expression of 84 kinds of mouse cytokines is detected, wherein making with Cytokine Expression Level in control group tissue
For control.
84 kinds of cytokine up regulation lower the analysis of situation thermal map as shown in Figure 1B, specifically raise multiple such as Fig. 1 C institute
Show.The result shows that ABPS processing group is compared with the control group, up-regulation gene (Fold > 2) shares 10, comprising: Bmp3, Csf2,
Ifnb1, Il15, Il17c, Il17f, Il2, Il23a, Il5 and Inhba；Down-regulated gene (Fold < -2) totally 9, comprising:
Cd40lg, Il10, Il13, Il16, Il1b, Lta, Ltb, Tnf and Tnfsf8.The result shows that Inokopolyose normal mouse seemingly
There is slight immunostimulation.
2 ABPS of embodiment is to the prevention effect for inducing mouse colorectal cancer
It has been reported that the killing that ABPS stimulation DC can cooperate with CIK to improve to Human colorectal cancer cells strain SW480 is lived
Property, but ABPS does not in vivo report the inhibiting effect of colorectal cancer also.The present embodiment uses oxidized azoethane/Portugal poly- first
Sugared sodium sulphate (AOM/DSS) method constructs inflammation associated colorectal cancer model, in order to further investigate ABPS to induction mouse knot
The prevention effect of the carcinoma of the rectum carries out ABPS stomach-filling processing to mouse during modeling, by time point as shown in Figure 2 A stomach-filling weekly
Once, synchronous with Fig. 1 holding.Specifically, C57BL/6 mouse is divided into two groups, every group 10, and using oxidized azoethane/
The inflammation associated colorectal cancer model of dextran sulfate sodium (AOM/DSS) inducing mouse, during which carry out stomach-filling processing: experimental group is pressed
200mg/kg Inokopolyose stomach-filling processing, control group carry out stomach-filling processing with sterile water.Mouse is removed after experiment
Colon and rectum processing, and tumor formation number in each group mouse Colon and rectum is counted.For the anti-colorectal carcinoma for further analyzing ABPS
Effect whether to influence the expression of cell factor it is related, research Inokopolyose to induction mouse junction cancer elemental abundances,
And inquire into its possible mechanism of action.The present embodiment carries out PCR Array analysis to cancerous tissue, is examined using PCR Array method
Survey the expression of 84 kinds of mouse cytokines.
As a result, it has been found that colorectal cancer tumor formation number is far less than control group (as shown in Figure 2 B) in ABPS stomach-filling processing group.84
It plants cytokine up regulation or the analysis of downward situation thermal map as shown in Figure 2 C and it particularly adjusts multiple as shown in Figure 2 D.ABPS
Compared with the control group, up-regulation gene (Fold > 2) shares 7 to processing group, comprising: Adipoq, Csf3, Il10, Il24, Il5, Il6
And Inha；Down-regulated gene (Fold < -2) totally 3, comprising: Il13, Il23a and Spp1.
The result shows that ABPS has significant prevention effect to colorectal cancer, it being capable of pre- preventing tumor generation.Inokopolyose exists
The tumor prevention effect of colorectal cancer model mice may be by the generation by inhibiting IL23 and enteritis.
It discusses
ABPS has good prevention effect to inflammatory induction colorectal cancer, while its mechanism of action is likely to and cell
The expression of the factor is related.Present invention finds some possible relevant cell factors at present, next will verify this by qPCR
The authenticity of a little differential genes, and the specific mechanism of action of ABPS is further illustrated by cell strain level.
All references mentioned in the present invention is incorporated herein by reference, independent just as each document
It is incorporated as with reference to such.In addition, it should also be understood that, after reading the above teachings of the present invention, those skilled in the art can
To make various changes or modifications to the present invention, such equivalent forms equally fall within model defined by the application the appended claims
It encloses.
Claims (10)
1. a kind of purposes of Inokopolyose, which is characterized in that be used to prepare the promotor of cell factor, or be used to prepare a preparation
Or composition, the preparation or composition are used to promoting or raising the cytokine-expressing in cell,
Wherein, the cell factor is selected from the group: Bmp3, Csf2, Ifnb1, Il15, Il17c, Il17f, Il2, Il23a,
Il5, Inhba, Adipoq, Csf3, Il10, Il24, Il6, Inha, or combinations thereof.
2. purposes as described in claim 1, which is characterized in that the cell factor comes from enterocyte.
3. purposes as described in claim 1, which is characterized in that the cell includes normal cell；And/or
The cell factor is selected from the group: Bmp3, Csf2, Ifnb1, Il15, Il17c, Il17f, Il2, Il23a, Il5,
Inhba, or combinations thereof.
4. purposes as described in claim 1, which is characterized in that the cell includes cancer cell；And/or
The cell factor is selected from the group: Adipoq, Csf3, Il10, Il24, Il5, Il6, Inha, or combinations thereof.
5. a kind of purposes of Inokopolyose, which is characterized in that be used to prepare the inhibitor of cell factor, or be used to prepare a preparation
Or composition, the preparation or composition are used to inhibiting or lowering the cytokine-expressing in cell,
Wherein, the cell factor is selected from the group: Cd40lg, Il10, Il13, Il16, Il1b, Lta, Ltb, Tnf,
Tnfsf8, Il23a, Spp1, or combinations thereof.
6. purposes as claimed in claim 5, which is characterized in that the cell factor comes from enterocyte.
7. purposes as claimed in claim 5, which is characterized in that the cell includes normal cell；And/or
The cell factor is selected from the group: Cd40lg, Il10, Il13, Il16, Il1b, Lta, Ltb, Tnf, Tnfsf8 or its group
It closes.
8. purposes as claimed in claim 5, which is characterized in that the cell includes cancer cell；And/or
The cell factor is selected from the group: Il13, Il23a, Spp1, or combinations thereof.
9. a kind of purposes of Inokopolyose, which is characterized in that be used to prepare the pharmaceutical composition or system of prevention and/or treating cancer
Agent.
10. purposes as claimed in claim 9, which is characterized in that the cancer is colorectal cancer, and preferably inflammatory knot is straight
Intestinal cancer.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810211374.6A CN110269864A (en) | 2018-03-14 | 2018-03-14 | Application of the Inokopolyose in anti-colorectal carcinoma |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201810211374.6A CN110269864A (en) | 2018-03-14 | 2018-03-14 | Application of the Inokopolyose in anti-colorectal carcinoma |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105377310A (en) * | 2013-07-23 | 2016-03-02 | 豪夫迈·罗氏有限公司 | Model of colorectal cancer |
| CN105859904A (en) * | 2016-04-29 | 2016-08-17 | 南京安吉生物科技有限公司 | Achyranthes aspera stem and/or leaf and/or root extract and extraction method and application thereof |
-
2018
- 2018-03-14 CN CN201810211374.6A patent/CN110269864A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105377310A (en) * | 2013-07-23 | 2016-03-02 | 豪夫迈·罗氏有限公司 | Model of colorectal cancer |
| CN105859904A (en) * | 2016-04-29 | 2016-08-17 | 南京安吉生物科技有限公司 | Achyranthes aspera stem and/or leaf and/or root extract and extraction method and application thereof |
Non-Patent Citations (3)
| Title |
|---|
| LI-QIN JIN等: "Opposite effects on tumor growth depending on dose of Achyranthes bidentata polysaccharides in C57BL/6 mice", 《INTERNATIONAL IMMUNOPHARMACOLOGY》 * |
| 周智东等: "牛膝多糖刺激的DC联合CIK细胞对SW480的杀伤作用研究", 《中国中药杂志》 * |
| 李佃贵: "《李佃贵浊毒理论临床经验实录丛书 胃癌浊毒论》", 31 October 2016, 中国科学技术出版社 * |
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