CN116672369A - Use of bifidobacterium adolescentis in preparation of products for preventing and/or treating colorectal cancer - Google Patents
Use of bifidobacterium adolescentis in preparation of products for preventing and/or treating colorectal cancer Download PDFInfo
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
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Abstract
The invention belongs to the technical field of probiotics, and particularly relates to application of bifidobacterium adolescentis ATCC15703 in preparation of products for preventing and/or treating colorectal cancer. According to the invention, bifidobacterium adolescentis ATCC15703 can activate Wnt channels of CD143+ tumor-related fibroblasts in colorectal cancer to promote GAS1 secretion; but also can activate TLR2 and YAP by increasing the quantity of macrophages in intestinal tracts so as to promote DCN secretion and improve tumor microenvironment in various aspects. The bifidobacterium adolescentis ATCC15703 has remarkable cancer inhibition effect and definite cancer inhibition mechanism, can be used as probiotics to be applied singly or in combination with immune checkpoint inhibitors clinically, and provides a new strategy for preventing or treating colorectal cancer.
Description
Technical Field
The invention belongs to the technical field of probiotics, and particularly relates to application of bifidobacterium adolescentis ATCC15703 in preparation of products for preventing and/or treating colorectal cancer.
Background
China is a country with high colorectal cancer incidence rate, the second most frequently seen in all tumors, and the fifth most frequently seen in mortality rate, so that the national health is seriously endangered. Colorectal cancer is mainly caused by genetic factors and environmental factors, and many clinical studies have found that intestinal flora is highly correlated with the occurrence and development of colorectal cancer. The existing clinical treatment scheme of colorectal cancer has strong side effect, high price and low efficiency, and causes serious burden on medical treatment in China, so that the exploration of a high-efficiency and low-cost control method is urgent.
Probiotics are living microorganisms that, when ingested in appropriate amounts, exert beneficial effects on the health of the consumer, and are an important component of the intestinal microenvironment. Probiotics are believed to inhibit the development of colorectal cancer by participating in host metabolism, maintaining intestinal barrier integrity, and regulating host immunity. However, most of the research is only remained in the correlation of intestinal flora and colorectal cancer, and key strains and action mechanisms thereof are not clearly identified. Therefore, a strain capable of clearly inhibiting colorectal cancer is screened, and can be combined with the existing clinical treatment means to prepare a product for preventing and/or treating colorectal cancer so as to achieve the aim of better preventing and/or treating colorectal cancer.
Bifidobacterium adolescentis is a completely anaerobic gram-positive bacterium in the normal intestinal tract of an adult, can autonomously reproduce, maintain the balance of intestinal flora and regulate the intestinal homeostasis of the human body. Bifidobacterium adolescentis has certain application in foods and medicines, such as improving acute and chronic diarrhea, constipation and inflammatory bowel disease, delaying aging, etc.
Disclosure of Invention
The first object of the present invention is to provide the use of bifidobacterium adolescentis ATCC15703 in the preparation of a product for the prevention and/or treatment of colorectal cancer.
Bifidobacterium adolescentis ATCC15703 is a whole genome sequencing strain isolated from the intestinal tract of adults and is a standard strain of bifidobacterium adolescentis from ATCC.
The invention can also adopt or combine the following technical proposal when adopting the technical proposal:
as a preferred technical scheme of the invention: the bifidobacterium adolescentis ATCC15703 has the following properties:
(1) Increasing the number of cd143+ tumor-associated fibroblasts;
(2) Promote secretion of CD143+ tumor-associated fibroblasts GAS 1;
(3) Increasing the number of macrophages;
(4) Promote the secretion of DCN by macrophages.
As a preferred technical scheme of the invention: the product is a medicine, a health food or a food;
the medicine comprises a medicine carrier and/or pharmaceutically acceptable auxiliary materials;
the dosage forms of the medicine or the health food comprise pills, tablets, powder, capsules, granules, suspension, injection, oral liquid, enema or tube feeding preparation;
the food comprises special medical food, solid beverage, dietary fiber, dairy product, bean product, cake or animal feed.
The second object of the present invention is to provide the use of bifidobacterium adolescentis ATCC15703 in the preparation of immune checkpoint inhibitor sensitizers.
The invention can also adopt or combine the following technical proposal when adopting the technical proposal:
as a preferred technical scheme of the invention: the immune checkpoint inhibitor is an anti-PD-1 antibody.
Specifically, the sensitizer prepared by bifidobacterium adolescentis ATCC15703 is orally taken and the anti-PD-1 antibody is injected.
The third object of the present invention is to provide the use of bifidobacterium adolescentis ATCC15703 in the preparation of TLR2 expression promoting agents, YAP expression promoting agents, GAS1 expression promoting agents or DCN secretion promoting agents.
A fourth object of the present invention is to provide the use of bifidobacterium adolescentis ATCC15703 in increasing the number of cd143+ tumour-associated fibroblasts and/or in promoting the secretion of cd143+ tumour-associated fibroblasts GAS 1.
It is a further object of the present invention to provide the use of bifidobacterium adolescentis ATCC15703 in increasing the number of macrophages and/or in promoting the secretion of DCN by macrophages.
The invention has at least the following advantages and beneficial effects:
(1) The bifidobacterium adolescentis ATCC15703 improves the tumor microenvironment from various aspects, has obvious effect of inhibiting colorectal cancer growth, has no relevant documents and patent reports at present, and can be used as a beneficial supplement of the current limited probiotic treatment means;
(2) The bifidobacterium adolescentis ATCC15703 can activate Wnt channels of the bifidobacterium adolescentis by increasing the quantity of CD143+ tumor-related fibroblasts in colorectal cancer so as to promote the secretion of GAS1, and can activate TLR2 and YAP by increasing the quantity of macrophages in intestinal tracts so as to promote the secretion of DCN, so that a cancer inhibition mechanism is clear, a signal channel is clear, and side effects can be effectively avoided or reduced by reasonable clinical application;
(3) Bifidobacterium adolescentis ATCC15703 takes cd143+ tumor-associated fibroblasts and dcn+ tumor-associated macrophages as downstream important targets, wherein both cd143+ tumor-associated fibroblasts and dcn+ tumor-associated macrophages are defined for the first time, and cd143+ tumor-associated fibroblasts up-regulate GAS1 expression by activating wnt signaling pathways, thereby inhibiting colorectal cancer; dcn+ tumor-associated macrophages up-regulate DCN expression via the TLR2/YAP axis, thereby inhibiting colorectal cancer. The invention provides new clues and new ideas for exploring the tumor microenvironment in the future.
Drawings
FIG. 1 shows the cancer inhibiting effect of bifidobacterium adolescentis ATCC15703 in a mouse AOM-DSS tumor model in example 1.
FIG. 2 shows that bifidobacterium adolescentis ATCC15703 increases the number of CD143+ tumor-associated fibroblasts in example 2; in the figure, A is single cell sequencing data tSNE dimension-reducing tumor-associated fibroblasts; b is composed of 5 tumor-associated fibroblast subpopulations derived from bifidobacterium adolescentis ATCC15703 or PBS group; c is the expression level of in vitro PBS, bifidobacterium adolescentis ATCC15703 and escherichia coli treated tumor-associated fibroblast CD143 detected by western; d is a statistical plot of tumor size of bifidobacterium adolescentis ATCC 15703-treated tumor-associated fibroblasts in a subcutaneous tumor model.
FIG. 3 shows that bifidobacterium adolescentis ATCC15703 inhibits tumor growth by upregulating CD143+ tumor-associated fibroblast GAS1 expression in example 3; in the figure, A is the expression level of CD143+ and CD 143-tumor associated fibroblast GAS1 in single cell sequencing data; b is the expression level of tumor-associated fibroblast GAS1 detected by western in vitro PBS, bifidobacterium adolescentis ATCC15703 and treated by escherichia coli; c is a statistical plot of tumor size of tumor-associated fibroblasts overexpressing GAS1 in a subcutaneous tumor model.
FIG. 4 shows that bifidobacterium adolescentis ATCC15703 inhibits tumor growth by increasing the number of intestinal macrophages in mice with an AOM-DSS tumor model in example 4. In the figure, A is the number of intestinal macrophages of mice with the model of AOM-DSS tumor, which is found by detecting bifidobacterium adolescentis ATCC15703 through flow cytometry; b is a statistical plot of tumor size of bifidobacterium adolescentis ATCC 15703-treated macrophages in a subcutaneous tumor model.
FIG. 5 shows that bifidobacterium adolescentis ATCC15703 inhibits tumor growth by up-regulating the secretion of DCN in macrophages in example 5; in the figure, A is bifidobacterium adolescentis ATCC15703 increasing secretion of macrophage DCN; b is a macrophage treated by bifidobacterium adolescentis ATCC15703 and plays a role in inhibiting cancer by up-regulating DCN; c is a cell line for stably knocking out DCN on a macrophage line Raw264.7, and then verification of in vivo cancer inhibition effect of bifidobacterium adolescentis ATCC15703 under the condition of knocking down the DCN is carried out.
FIG. 6 is a graph showing that bifidobacterium adolescentis ATCC15703 upregulates macrophage DCN secretion by the TLR2/YAP axis in example 6; in the figure, A is the western detection of expression of PBS, bifidobacterium adolescentis ATCC 15703-treated macrophages TLR2, YAP and DCN; b is the level of TLR2, YAP and DCN before and after the western detection of the TLR2 inhibitor Cu-CPT22 treatment; c is western detection of TLR2, YAP and DCN levels before and after treatment with the YAP inhibitor verteporfin.
FIG. 7 shows the effect of bifidobacterium adolescentis ATCC15703 on the increase of anti-PD-1 antibody immunotherapy in example 7.
Detailed Description
The invention will be described in further detail with reference to the drawings and specific embodiments.
Example 1: bifidobacterium adolescentis ATCC15703 inhibiting colorectal cancer growth in vivo
The 6 week male C57BL/6 mice were randomly divided into 3 groups of 9. The mice drink water containing 2mg/mL streptomycin for 1 week to primarily remove intestinal flora, which is beneficial to the colonization of the transplanted bacteria. After the intestinal flora is cleared, three groups are respectively irrigated with PBS, escherichia coli and bifidobacterium adolescentis ATCC15703, and the dosage is 1 multiplied by 10 9 CFU/mouse, lavage volume 200. Mu.L, once daily. AOM was intraperitoneally injected at a dose of 10mg/kg and given three rounds of 2.5% dss free drink for five days, 14 days apart. The molding process focuses on weight change, fecal molding, hematochezia and rectocele of mice. After the molding is finished, counting the number and the size of colorectal tumors.
As shown in fig. 1, supplementing bifidobacterium adolescentis ATCC15703 can significantly reduce the number of intestinal tumors in AOM-DSS model mice and reduce tumor burden.
Example 2: bifidobacterium adolescentis ATCC15703 inhibits tumor growth by increasing the number of cd143+ tumor-associated fibroblasts in tumors
The intestinal tumors of AOM-DSS cancer model mice were lysed into single cells using collagenase type IV by modelling as described in example 1, and the transcript levels of each cell were detected by single cell transcriptome sequencing. And (3) projecting all the obtained cell transcription level matrixes to a two-dimensional plane by adopting a tSNE dimension reduction mode, and classifying and grouping the obtained two-dimensional dot patterns by combining an on-line database and a recognized cell marker gene according to marker genes obtained by each group. Further dimension reduction analysis is carried out on the tumor fibroblasts in the same manner to obtain C1-C5 group tumor-related fibroblasts, the composition of the tumor-related fibroblasts of each subgroup of bifidobacterium adolescentis ATCC15703 group and PBS group is compared, the bifidobacterium adolescentis ATCC15703 is found to obviously increase the C4 subgroup in the tumor, the marker gene of the C4 subgroup is further defined as CD143, and then the results of single cell sequencing are verified through flow cytometry and western.
The cancer inhibiting function of cd143+ fibroblasts was subsequently validated in a subcutaneous tumor model. Tumor-associated fibroblasts from colorectal cancer patients were incubated with bifidobacterium adolescentis ATCC15703 (moi=10:1) for 48 hours and then washed 3 times with PBS. Tumor-associated fibroblasts treated with PBS or bifidobacterium adolescentis ATCC15703 were then combined with 3X 10 6 HCT-116 cells were mixed and injected subcutaneously into nude mice (100. Mu.L per mouse). Tumor volumes were monitored every two days after 7 days of injection and the calculation formula was as follows: volume=0.54×l×w 2 Where L is the longest diameter and W is the shortest diameter. At the end stage, tumor weights were recorded.
As shown in fig. 2, supplementation with bifidobacterium adolescentis ATCC15703 increased the number of cd143+ tumor-associated fibroblasts in the tumor and bifidobacterium adolescentis ATCC 15703-treated tumor-associated fibroblasts were able to inhibit tumor growth of HCT-116 cells in vivo.
Example 3: bifidobacterium adolescentis ATCC15703 inhibits tumor growth by upregulating cd143+ tumor-associated fibroblast GAS1 expression
Single cell transcriptome sequencing data were analyzed for differences in cd143+ tumor-associated fibroblasts and CD 143-tumor-associated fibroblast transcriptome levels. Fresh tumor or normal colon tissue was cut into small pieces of 2mm diameter in vitro and then inoculated into a flask containing DMEM medium (medium containing 20% fetal bovine serum and 1% penicillin/streptomycin). The flask was inverted and incubated at 37℃with 5% CO 2 Hold down for 4 hours, then invert the flask. Adherent cells were continuously cultured in DMEM medium containing 20% fbs for about 3To 4 weeks. The medium was changed every three days. Bifidobacterium adolescentis ATCC15703 was then added to purified tumor-associated fibroblasts at moi=1:100, and after 24h incubation the protein was extracted and the expression of GAS1 in tumor-associated fibroblasts was detected by western analysis.
The fibroblast line NIH/3T3 was overexpressed GAS1 using Cas9 technology, then compared to 3X 10 6 MC38 cells (moi=10:1) were mixed injected (100 μl per mouse) subcutaneously into nude mice. After 7 days of implantation, tumor volumes were monitored every 2 days, and the calculation formula was as follows: volume=0.54×l×w 2 Where L is the longest diameter and W is the shortest diameter. At the end stage, tumor weights were recorded.
As shown in fig. 3, supplementation with bifidobacterium adolescentis ATCC15703 was able to increase expression of cd143+ tumor-associated fibroblasts GAS1 in vivo as well as in vitro. Tumor-associated fibroblasts that overexpress GAS1 are capable of inhibiting tumor growth of MC38 cells in vivo.
Example 4: bifidobacterium adolescentis ATCC15703 inhibits tumour growth by increasing the number of macrophages in the intestinal tract
Taking PBS, bifidobacterium adolescentis ATCC15703 or AOM-DSS mouse colon tissue of escherichia coli intragastric administration on ice, removing adipose tissue and a system membrane, placing in a precooling 1640 culture medium, longitudinally cutting, washing with 1640 culture medium for 2-3 times, washing mucus, and keeping the cutting intestinal position and length of each group as consistent as possible (about 3 cm). Cutting intestinal tracts into 5-6 small sections, placing each section with the length of about 0.5cm in intestinal epithelial digestion liquid preheated at 37 ℃ (intestinal epithelial separation liquid formula: D-Hanks solution+5% inactivated FBS+1mM DTT+5mM EDTA), placing on a shaking table, incubating at 37 ℃ for 20-30min at 150rpm, vigorously shaking, pouring out the liquid on absorbent paper, clamping the intestinal tracts into a new centrifuge tube by forceps, adding 1640 culture medium, and fully shaking and washing for 2-3 times. The intestinal segments were then minced to 1mm pieces, collected in a new tube, and 5mL of lamina propria digest (lamina propria digest formula: hanks solution+5% inactivated FBS+1mg/mL type four collagenase) was added and placed in a shaker at 37℃for 30min at 200 rpm. After completion, the mixture was filtered through a 300-mesh filter into a 15-mL centrifuge tube, and the supernatant was centrifuged at 700g for 5 min. Then the cell concentration was adjusted: the collected single cell suspension was thinned with PBSThe cell number is regulated to 2 multiplied by 10 7 /mL. After adding 0.3 mu L of dead and live antibody to 50 mu L of each sample, the mixture was incubated at 4℃for 30min in the absence of light, and then staining was stopped by adding 150 mu L of FACS buffer, centrifuging at 700g for 5min, discarding the supernatant, and re-suspending at 50 mu LPBS. Antibody premix (FVS 510 (564406), alexa Fluor 700-CD45 (560510), BV421-F4/80 (565411), AF488-CD11b (557672) and PECPCY5.5-CD3 (551163)) was prepared, mixed well with the appropriate amount of antibody per sample, incubated at 4℃for 30min in the dark, terminated by adding 150. Mu.L PBS, centrifuged at 700g for 5min, the supernatant discarded, washed 1 time with 150. Mu.L PBS, and resuspended in the appropriate volume.
Next we validated the function of the macrophages treated with bifidobacterium adolescentis ATCC15703 using the subcutaneous tumor model. With human macrophage cell line THP-1, 10cm dishes were plated at appropriate density and stimulated to differentiate maturation with 200nM phorbol ester. Then, a proper amount of macrophages are uniformly spread in a 6-well plate, and after cells are attached, bifidobacterium adolescentis ATCC15703 is added into the macrophages for co-culture for 24 hours at a moi=100:1. Then combining PBS or Bifidobacterium adolescentis ATCC 15703-treated macrophages with 3X 10 6 HCT-116 cells were mixed and injected subcutaneously into nude mice (100. Mu.L per mouse). Tumor volumes were monitored every two days after 7 days of injection and the calculation formula was as follows: volume=0.54×l×w 2 Where L is the longest diameter and W is the shortest diameter. At the end stage, tumor weights were recorded.
As shown in fig. 4, flow cytometry found that bifidobacterium adolescentis ATCC15703 increased the number of macrophages in the intestinal tract of AOM-DSS model mice and that bifidobacterium adolescentis ATCC 15703-treated macrophages were able to inhibit tumor growth of HCT-116 in vivo.
Example 5: bifidobacterium adolescentis ATCC15703 inhibits tumor growth by up-regulating secretion of DCN in macrophages
The C57BL/6 mice were sacrificed by cervical dislocation, then transferred to a super clean bench, and the bilateral femur and tibiofibular bone of the mice were stripped. 2-3mL of culture medium (containing double antibodies) is added into a 10cm dish, two ends of femur and tibia are cut off, a bone marrow cavity is exposed, the culture medium is sucked by a 1mL syringe, the bone marrow cavity is repeatedly flushed in the 10cm dish, and bone marrow cells in the bone marrow cavity are flushed out. The washed cell suspension was filtered with a 70 μm filter, centrifuged at 1000rpm for 5min, and the supernatant was discarded. Cells were resuspended in DMEM medium containing 1% of green streptomycin, 10% FBS and 25ng/mL M-CSF and cultured for 5 days to induce differentiation. The number and purity of extracted macrophages were identified by flow cytometry. Appropriate amount of macrophages were plated uniformly in 6-well plates, and after cell attachment, the medium containing the diabodies was changed to DMEM medium without antibodies containing 10% fbs. Bifidobacterium adolescentis ATCC15703 was added to macrophages at moi=100:1 for co-cultivation for 24h, after which the RNA from the macrophages was collected and submitted to transcriptome sequencing. Intersection of the differential gene from in vitro transcriptome sequencing with the differential gene from in vivo single cell sequencing revealed that the most significant up-regulation of DCN expression, followed by western detection of macrophage DCN expression after treatment with bifidobacterium adolescentis ATCC15703, was used to verify relevant sequencing data.
The DCN gene was further knocked out in a murine Raw264.7 cell line using Cas9 technology, and then co-injected subcutaneously with HCT-116 cells as described in example 4 to detect tumor size and weight.
As shown in FIG. 5, bifidobacterium adolescentis ATCC15703 increases secretion of macrophage DCN in vivo and in vitro, and the macrophage after knocking out the DCN gene is not able to inhibit growth of HCT-116 subcutaneous tumor in vivo by co-treatment with bifidobacterium adolescentis ATCC 15703.
Example 6: bifidobacterium adolescentis ATCC15703 treated macrophages up-regulate the expression of DCN through TLR2 and YAP
In the co-culture manner shown in example 5, it was found that the TLR2 and YAP of macrophages treated with bifidobacterium adolescentis ATCC15703 were up-regulated, and then TLR2 inhibitors Cu-CPT22 and YAP inhibitor verteporfin were added during co-culture of bifidobacterium adolescentis ATCC15703 and macrophages, respectively, and the expression of macrophages TLR2, YAP and DCN was examined by western analysis.
The results are shown in FIG. 6, where bifidobacterium adolescentis ATCC 15703-treated macrophages up-regulate the secretion of DCN through the TLR2/YAP axis.
Example 7: therapeutic effect of bifidobacterium adolescentis ATCC 15703-sensitized anti-PD-1 antibodies in colorectal cancer
The 6-week-old male C57BL/6 mice were randomly divided into 4 groups of 10 PBS+isotype, PBS+anti-PD-1, bifidobacterium adolescentis ATCC15703+isotype, and Bifidobacterium adolescentis ATCC 15703+anti-PD-1, respectively. PBS was the solvent for Bifidobacterium adolescentis ATCC15703, the solvent control without Bifidobacterium adolescentis ATCC15703, isotype was the same source of antibody as the anti-PD-1 antibody, but it had no anti-PD-1 activity, and was the negative isotype control for the anti-PD-1 antibody. The mice can drink water containing 2mg/mL metronidazole, 2mg/mL penicillin, 2mg/mL streptomycin and 1mg/mL vancomycin freely before molding, and intestinal flora is primarily cleared for 1 week, so that the transplanting bacteria colonization is facilitated.
After the intestinal flora is cleared, the bifidobacterium adolescentis + isotype group and the bifidobacterium adolescentis + anti-PD-1 antibody group are administered to the bifidobacterium adolescentis for gastric lavage, and the remaining two groups of PBS are used for gastric lavage, wherein the dosage is 1 multiplied by 10 9 CFU/mouse, lavage volume 200. Mu.L, once daily. After 7 days of gastric lavage, 2X 10 7 Is injected subcutaneously into mice (100 μl per mouse). After 10 days of injection, the PBS group and bifidobacterium adolescentis ATCC15703 group were injected intraperitoneally with IgG Isotype or with anti-PD-1 antibody (100. Mu.g each) by injecting every two days, and tumor volumes were monitored every two days as follows: volume=0.54×l×w 2 Where L is the longest diameter and W is the shortest diameter. The experiment was terminated every other day after three PD-1 treatments, and tumor weights were recorded and counted.
The results are shown in FIG. 7, where the tumor size of the bifidobacterium adolescentis ATCC15703+ anti-PD-1 antibody group is significantly smaller than that of the PBS+ anti-PD-1 antibody group, and bifidobacterium adolescentis ATCC15703 significantly increases the therapeutic effect of PD-1.
The above detailed description is intended to illustrate the present invention by way of example only and not to limit the invention to the particular embodiments disclosed, but to limit the invention to the precise embodiments disclosed, and any modifications, equivalents, improvements, etc. that fall within the spirit and scope of the invention as defined by the appended claims.
Claims (8)
1. Use of bifidobacterium adolescentis ATCC15703 in the preparation of a product for the prevention and/or treatment of colorectal cancer.
2. The use according to claim 1, characterized in that: the bifidobacterium adolescentis ATCC15703 has the following properties:
(1) Increasing the number of cd143+ tumor-associated fibroblasts;
(2) Promote secretion of CD143+ tumor-associated fibroblasts GAS 1;
(3) Increasing the number of macrophages;
(4) Promote the secretion of DCN by macrophages.
3. Use according to claim 1 or 2, characterized in that: the product is a medicine, a health food or a food;
the medicine comprises a medicine carrier and/or pharmaceutically acceptable auxiliary materials;
the dosage forms of the medicine or the health food comprise pills, tablets, powder, capsules, granules, suspension, injection, oral liquid, enema or tube feeding preparation;
the food comprises special medical food, solid beverage, dietary fiber, dairy product, bean product, cake or animal feed.
4. Use of bifidobacterium adolescentis ATCC15703 in the preparation of an immune checkpoint inhibitor sensitizer.
5. The use according to claim 4, characterized in that: the immune checkpoint inhibitor is an anti-PD-1 antibody.
6. Use of bifidobacterium adolescentis ATCC15703 in the preparation of a TLR2 expression promoter, a YAP expression promoter, a GAS1 expression promoter or a DCN secretion promoter.
7. Use of bifidobacterium adolescentis ATCC15703 for increasing the number of cd143+ tumour-associated fibroblasts and/or for promoting secretion of cd143+ tumour-associated fibroblasts GAS 1.
8. Use of bifidobacterium adolescentis ATCC15703 for increasing the number of macrophages and/or for promoting the secretion of DCN by macrophages.
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