CN106729654B - Application of cyclooxygenase-2 and inhibitor thereof in bladder cancer - Google Patents
Application of cyclooxygenase-2 and inhibitor thereof in bladder cancer Download PDFInfo
- Publication number
- CN106729654B CN106729654B CN201710062425.9A CN201710062425A CN106729654B CN 106729654 B CN106729654 B CN 106729654B CN 201710062425 A CN201710062425 A CN 201710062425A CN 106729654 B CN106729654 B CN 106729654B
- Authority
- CN
- China
- Prior art keywords
- cyclooxygenase
- bladder cancer
- inhibitor
- cells
- cox
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/423—Oxazoles condensed with carbocyclic rings
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y303/00—Hydrolases acting on ether bonds (3.3)
- C12Y303/02—Ether hydrolases (3.3.2)
- C12Y303/02003—Epoxide hydrolase (3.3.2.3)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses cyclooxygenase-2 and an application of a cyclooxygenase-2 inhibitor in bladder cancer, and finds that nimesulide serving as a selective inhibitor of cyclooxygenase-2 can inhibit the proliferation of bladder cancer cells T24 by down-regulating the expression of cyclooxygenase-2; and four inhibitors of the cyclooxygenase-2 are obtained by screening the model, and all the four inhibitor compounds are 2-aminobenzoxazole derivatives which can lower the expression of the cyclooxygenase-2 and inhibit the proliferation of T24. The invention proves that the cyclooxygenase-2 can be used as a drug target for screening drugs for inhibiting bladder cancer.
Description
Technical Field
The invention belongs to medicine, relates to discovery of a bladder cancer treatment target and development of a treatment medicine, and particularly relates to application of cyclooxygenase-2 and an inhibitor thereof in bladder cancer.
Background
Bladder cancer is a common malignant tumor of urinary system, and most of the cancers are transitional epithelial cell cancers. According to the statistics of the world health organization in 2002, about 36 million new cases occur globally every year, the incidence rate of the cases is ninth of malignant tumors, male patients account for about 75-80%, and the average incidence age is 70 years old; about 15 million people die each year from bladder cancer, with the 12 th leading in fatal cancers and, in non-therapeutic cases, a natural survival time of about 16 to 20 months. Clinically, intermittent painless hematuria is the earliest symptom of bladder cancer, well-differentiated papillary tumors can have severe hematuria, poorly-differentiated invasive cancers can have less hematuria, and non-epithelial tumors have less hematuria. Frequent micturition, urgency and other bladder irritation symptoms suggest possible carcinoma in situ of the bladder. However, other early bladder cancers are less likely to develop symptoms of urinary tract irritation if not accompanied by infection or tumor in the trigone area. Difficulty in urination or urinary retention can occur when tumors are large or block the bladder orifice. In the late stage, the lower abdomen infiltrative tumor may be affected, or severe anemia and edema may appear.
Cyclooxygenase (Cox) is a rate-limiting enzyme of prostaglandin synthesis during arachidonic acid metabolism, and has two isoenzymes, Cox-1 and Cox-2. Cox-1 is a structural enzyme, belongs to a normal component of a human body, and can be expressed in most tissues; cox-2 is an inducible enzyme, the gene length is about 8.8kb, and contains 10 exons and 9 introns, Cox-2 is not expressed in most tissues under normal physiological state, but is rapidly synthesized and activates inflammatory reaction under the stimulation of growth factors, cytokines, cancer promoters and the like, and long-term chronic inflammation can promote tumorigenesis and development. In a plurality of solid tumors such as cervical cancer, breast cancer, lung cancer, colon cancer and the like, the expression of Cox-2 is up-regulated, and the application of a Cox inhibitor can play a certain inhibition effect. cox inhibitors, also known as non-steroidal anti-inflammatory drugs, are one of the most widely used drugs worldwide, and mainly reduce the production of inflammatory mediators prostaglandin by inhibiting cox expression, thereby achieving the effects of anti-inflammation, analgesia and antipyresis.
2-aminobenzoxazole and derivatives thereof are typical heterocyclic compounds and have various activities, but the effects on cyclooxygenase-2 and bladder cancer are not reported at present.
Disclosure of Invention
The invention aims to provide the application of cyclooxygenase-2 and an inhibitor thereof in bladder cancer.
The above purpose of the invention is realized by the following technical scheme:
application of cyclooxygenase-2 and its inhibitor in preparing medicine for treating bladder cancer is disclosed.
Preferably, the inhibitor is a 2-aminobenzoxazole derivative.
Preferably, the 2-aminobenzoxazole derivative is one of the following derivatives 1 to 4:
derivative 1
Derivative 3
Derivative 4
The application of the pharmaceutical composition in preparing the medicine for treating bladder cancer comprises the inhibitor and a pharmaceutically acceptable carrier, and the pharmaceutical composition is prepared into a pharmaceutically acceptable dosage form.
Preferably, the pharmaceutically acceptable carrier comprises one or more solid, semi-solid or liquid excipients; the pharmaceutically acceptable dosage forms comprise tablets, capsules, granules, injections, pills, powder, paste and oral liquid preparations.
The invention has the beneficial effects that:
the invention discovers that nimesulide, a selective inhibitor of cyclooxygenase-2, can inhibit the proliferation of T24 of bladder cancer cells by down-regulating the expression of cyclooxygenase-2; and four inhibitors of the cyclooxygenase-2 are obtained by screening the model, and all the four inhibitor compounds are 2-aminobenzoxazole derivatives which can lower the expression of the cyclooxygenase-2 and inhibit the proliferation of T24. The invention proves that the cyclooxygenase-2 can be used as a drug target for screening drugs for inhibiting bladder cancer.
Drawings
FIG. 1 is a chemical structural formula of four 2-aminobenzoxazole derivatives 1-4;
FIG. 2 shows the inhibition rate of T24 cells (2B) and the Western Blot assay of COX-2 protein in T24 cells (2A) after the derivatives 1-4 were applied to T24 cells for 48 hours at different concentrations.
Detailed Description
The following examples further illustrate the essence of the present invention.
Example 1: effect of nimesulide on cyclooxygenase-2 expression and cell proliferation in bladder cancer cells
First, experimental material
The bladder cancer cell line T24 is stored for a long time by the company; methylsepizole blue MTT, dimethyl sulfoxide DMSO, DMEM medium and fetal bovine serum were purchased from Sigma. The others are conventional reagents.
Second, Experimental methods
1. Cell culture and Experimental groups
The bladder cancer cell line T24 was cultured according to a conventional method. DMEM culture medium containing 10% fetal calf serum at 37 deg.C and 5% CO2Culturing under saturated humidity, and changing the culture solution for 1 time in 48 h. Cells in the logarithmic growth phase were taken for the experiments. The experiment is divided into a control group and a nimesulide group, wherein the control group is not added with a cyclooxygenase-2 inhibitor, and the nimesulide group is added with nimesulide for treatment. The method comprises the following specific steps:
log phase bladder cancer cell line T24 as per 2 × 104The cells in each well are inoculated in a 96-well culture plate, and after 24 hours of culture, nimesulide with the final concentration of 50, 100 and 200 mu mol/L is added into the nimesulide group T24 cells for 48 hours of culture.
2. Expression assay of Cyclooxidase-2 (COX-2) in cells (Western Blot method)
Taking cells with nimesulide action for 48 hours, cracking the cells, extracting total protein, carrying out protein quantification by using a BCA method, taking 50 mu g of each group of protein for sampling, carrying out SDS-PAGE protein electrophoresis and transferring the protein to a PVDF membrane. The primary antibody is rabbit anti-human COX-2 polyclonal antibody with the dilution of 1:1000, and the polyclonal mouse anti-beta-actin antibody with the dilution of 1:2000, and is incubated overnight at 4 ℃. Adding goat anti-rabbit IgG marked by horseradish peroxidase and goat anti-mouse IgG marked by horseradish peroxidase respectively the next day, diluting at a ratio of 1:5000, and incubating at room temperature for 1 h. After washing, ECL chemiluminescence reagent is used for developing, the film is photographed after tabletting exposure, the optical density value of each strip is measured by a gel image processing system, and the ratio of COX-2/beta-actin is used as the relative expression quantity of the COX-2 protein.
3. Cell proliferation inhibition rate measurement
After 48h incubation, the absorbance (A) was measured in each well, 20. mu.l of MTT was added at 5mg/ml to each well before measurement, incubated for 4h, and after discarding the supernatant, 200. mu.l of DMSO was added to each well. Detection was carried out with a microplate reader at a wavelength of 560 nm. The average a value of each group was used to calculate the cell proliferation inhibition rate: the proliferation inhibition ratio (%) was (1-nimesulide group a/control group a) × 100%.
Third, experimental results
1. Morphological Effect of nimesulide on bladder cancer cell line T24
Compared with a control group, the nimesulide group has abnormal cell morphology, round and irregular cell bodies, wall detachment, loose cell-cell contact, increased particles in cytoplasm and slow proliferation. Over time, a portion of the cells slough off the culture plate walls.
2. Effect of nimesulide on Cyclooxidase-2 expression in bladder cancer cell line T24
The Western Blot result shows that under the condition that the gray scales of the beta-actin protein bands of the internal reference are basically consistent, the relative expression quantity of COX-2 protein in the nimesulide group is obviously reduced compared with the control group, and the result is shown in Table 1.
TABLE 1 relative expression levels of COX-2 proteins in each group after 48h of culture
3. Effect of nimesulide on inhibition rate of proliferation of bladder cancer cell line T24
MTT method test results show that nimesulide has obvious inhibition effect on the growth of T24 cells, and the inhibition effect and the drug concentration have obvious dependence, and the results are shown in Table 2.
TABLE 2 inhibition of proliferation of T24 cells in each group after 48h of culture
The results of example 1 indicate that cyclooxygenase-2 is likely to be the target of nimesulide inhibition of T24 cell proliferation, and nimesulide exerts its proliferation inhibition effect on bladder cancer cell line T24 by inhibiting the expression of cyclooxygenase-2.
Example 2: screening of cyclooxygenase-2 inhibitors
First, experimental material
The bladder cancer cell line T24 is stored for a long time by the company; methylsepizole blue MTT, dimethyl sulfoxide DMSO, DMEM medium and fetal bovine serum were purchased from Sigma. The others are conventional reagents.
Second, Experimental methods
1. Cell culture and Experimental groups
The bladder cancer cell line T24 was cultured according to a conventional method. DMEM culture medium containing 10% fetal calf serum at 37 deg.C and 5% CO2Culturing under saturated humidity, and changing the culture solution for 1 time in 48 h. Cells in the logarithmic growth phase were taken for the experiments. The experiment is divided into a control group and an administration group, wherein the control group is not added with a cyclooxygenase-2 inhibitor, and the administration group is added with different compounds to be tested for treatment. The method comprises the following specific steps:
log phase bladder cancer cell line T24 as per 2 × 104The cells/well were inoculated in 96-well culture plates and cultured for 24 hours, and then test compounds at different final concentrations were added to the administered group of T24 cells and cultured for 48 hours. The structures of the compounds to be tested are shown in Table 3 and FIG. 1.
TABLE 3 Structure of test Compounds
2. Determination of inhibition of cell proliferation, IC50 (concentration of compound at 50% inhibition) was calculated
After 48h incubation, the absorbance (A) was measured in each well, 20. mu.l of MTT was added at 5mg/ml to each well before measurement, incubated for 4h, and after discarding the supernatant, 200. mu.l of DMSO was added to each well. Detection was carried out with a microplate reader at a wavelength of 560 nm. The average a value of each group was used to calculate the cell proliferation inhibition rate: the proliferation inhibition ratio (%) was (1-dose group a/control group a) × 100%.
3. Expression assay of Cyclooxidase-2 (COX-2) in cells (Western Blot method)
Taking cells acted by a compound to be detected for 48 hours, extracting total protein after cell lysis, carrying out protein quantification by using a BCA method, taking 50 mu g of protein in each group, loading the protein, carrying out SDS-PAGE protein electrophoresis, and transferring the protein to a PVDF membrane. The primary antibody is rabbit anti-human COX-2 polyclonal antibody with the dilution of 1:1000, and the polyclonal mouse anti-beta-actin antibody with the dilution of 1:2000, and is incubated overnight at 4 ℃. Adding goat anti-rabbit IgG marked by horseradish peroxidase and goat anti-mouse IgG marked by horseradish peroxidase respectively the next day, diluting at a ratio of 1:5000, and incubating at room temperature for 1 h. After washing, ECL chemiluminescence reagent is used for developing, the film is photographed after tabletting exposure, the optical density value of each strip is measured by a gel image processing system, and the ratio of COX-2/beta-actin is used as the relative expression quantity of the COX-2 protein.
Third, experimental results
1. Proliferation inhibition rate and IC50 value of different compounds on T24 cells
MTT method detection results show that each compound has obvious inhibition effect on the growth of T24 cells, the inhibition effect and the drug concentration have obvious dependence, and IC50 values are shown in Table 4.
TABLE 42 aminobenzoxazole derivative IC50 values (μmol/L, action time 48h)
The inventor also tests the toxicity of the derivatives 1-4 to human normal bladder epithelial cells (SV-HUC-1 cell line, the action time is 24h), the cytotoxicity of the derivatives 1-3 is relatively high, the obvious cytotoxic effect appears at 120 mu mol/L (the inhibition rate is more than or equal to 20 percent compared with a control group, the same is shown below), and the inhibition rate of the derivative 4 is still less than 10 percent at 400 mu mol/L. The derivatives 1-3 can be developed into bladder cancer targeted drugs to reduce the damage to normal cells.
2. Effect of different Compounds on cyclooxygenase-2 expression in T24 cells
The Western Blot result shows that under the condition that the internal reference beta-actin protein band gray scale is basically consistent, the relative expression quantity of COX-2 protein in the administration group is obviously reduced compared with the control group, and the reduction degree is in a dependent relation with the administration dose. The inhibition rate of T24 cells and the Western Blot assay of COX-2 protein in T24 cells after the derivatives 1-4 (see Table 5) at different concentrations acted on T24 cells for 48 hours are shown in FIG. 2.
TABLE 5 derivatives 1-4 test concentration levels (μmol/L)
The invention discovers that nimesulide, a selective inhibitor of cyclooxygenase-2, can inhibit the proliferation of T24 of bladder cancer cells by down-regulating the expression of cyclooxygenase-2; and four inhibitors of the cyclooxygenase-2 are obtained by screening the model, and all the four inhibitor compounds are 2-aminobenzoxazole derivatives which can lower the expression of the cyclooxygenase-2 and inhibit the proliferation of T24. The invention proves that the cyclooxygenase-2 can be used as a drug target for screening drugs for inhibiting bladder cancer.
Claims (1)
1. The application of an cyclooxygenase-2 inhibitor in the preparation of a medicament for treating bladder cancer is characterized in that: the cyclooxygenase-2 inhibitor is one of the following structural compounds:
compound 1
Compound 2
Compound 3
Compound 4
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710062425.9A CN106729654B (en) | 2017-02-03 | 2017-02-03 | Application of cyclooxygenase-2 and inhibitor thereof in bladder cancer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710062425.9A CN106729654B (en) | 2017-02-03 | 2017-02-03 | Application of cyclooxygenase-2 and inhibitor thereof in bladder cancer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106729654A CN106729654A (en) | 2017-05-31 |
| CN106729654B true CN106729654B (en) | 2020-10-02 |
Family
ID=58956124
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710062425.9A Active CN106729654B (en) | 2017-02-03 | 2017-02-03 | Application of cyclooxygenase-2 and inhibitor thereof in bladder cancer |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106729654B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1468854A (en) * | 2003-07-02 | 2004-01-21 | 梅世昌 | Prepn process and use of substituted pyrazole compound |
| CN103333131A (en) * | 2013-06-26 | 2013-10-02 | 苏州奥索特新材料有限公司 | Preparation method of 2-aminobenzoxazole compound |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007109809A1 (en) * | 2006-03-23 | 2007-09-27 | Invitrogen Corporation | Methods and reagents for in vivo imaging of cancer cell lines |
-
2017
- 2017-02-03 CN CN201710062425.9A patent/CN106729654B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1468854A (en) * | 2003-07-02 | 2004-01-21 | 梅世昌 | Prepn process and use of substituted pyrazole compound |
| CN103333131A (en) * | 2013-06-26 | 2013-10-02 | 苏州奥索特新材料有限公司 | Preparation method of 2-aminobenzoxazole compound |
Non-Patent Citations (4)
| Title |
|---|
| Novel benzoxazole inhibitors of mPGES-1;Natasha Kablaoui等;《Bioorganic & Medicinal Chemistry Letters》;20121016;第907-911页 * |
| Synthesis and preliminary evaluation of 2-substituted-1,3-benzoxazole and 3-[(3-substituted)propyl]-1,3-benzoxazol-2(3H)-one derivatives as potent anticancer agents;M. S. R. Murty等;《Med Chem Res》;20100509;第576-586页 * |
| 张坚.环氧化酶2在膀胱癌发生发展以及治疗中的作用.《中国博士学位论文全文数据库 医药卫生科技辑》.2004, * |
| 环氧化酶2在膀胱癌发生发展以及治疗中的作用;张坚;《中国博士学位论文全文数据库 医药卫生科技辑》;20040915;第E072-85 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106729654A (en) | 2017-05-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Geng et al. | Ganoderic acid hinders renal fibrosis via suppressing the TGF-β/Smad and MAPK signaling pathways | |
| Basseri et al. | The chemical chaperone 4-phenylbutyrate inhibits adipogenesis by modulating the unfolded protein response [S] | |
| Zhang et al. | Ketogenic diet elicits antitumor properties through inducing oxidative stress, inhibiting MMP-9 expression, and rebalancing M1/M2 tumor-associated macrophage phenotype in a mouse model of colon cancer | |
| Tang et al. | A novel co-drug of aspirin and ursolic acid interrupts adhesion, invasion and migration of cancer cells to vascular endothelium via regulating EMT and EGFR-mediated signaling pathways: multiple targets for cancer metastasis prevention and treatment | |
| Yang et al. | Synthesis, anti-microbial and anti-inflammatory activities of 18β-glycyrrhetinic acid derivatives | |
| Ramana et al. | Mediation of aldose reductase in lipopolysaccharide-induced inflammatory signals in mouse peritoneal macrophages | |
| Feng et al. | Luteolin, an aryl hydrocarbon receptor ligand, suppresses tumor metastasis in vitro and in vivo | |
| Li et al. | Juglanin protects against high fat diet-induced renal injury by suppressing inflammation and dyslipidemia via regulating NF-κB/HDAC3 signaling | |
| KR101201956B1 (en) | Pharmaceutical composition for preventing and treating proliferating skin diseases and melanoma comprising pachastrissamine or salt there of as an active ingredient | |
| Dehghan et al. | Inhibitory effect of curcumin on angiogenesis in a streptozotocin-induced diabetic rat model: An aortic ring assay | |
| JP7466534B2 (en) | Compositions and methods for preventing and/or treating metabolic disorders and/or their clinical conditions - Patents.com | |
| JP4153663B2 (en) | Pharmaceutical composition comprising decursin | |
| Li et al. | Eriocitrin attenuates sepsis-induced acute lung injury in mice by regulating MKP1/MAPK pathway mediated-glycolysis | |
| Chen et al. | Sirtuin1 (SIRT1) is involved in the anticancer effect of black raspberry anthocyanins in colorectal cancer | |
| Kan et al. | Effect of Palrnatine on lipopolysaccharide-induced acute lung injury by inhibiting activation of the Akt/NF-κB pathway | |
| Xu et al. | Eupatilin inhibits xanthine oxidase in vitro and attenuates hyperuricemia and renal injury in vivo | |
| Vig-Varga et al. | Alpha-lipoic acid modulates ovarian surface epithelial cell growth | |
| CN106729654B (en) | Application of cyclooxygenase-2 and inhibitor thereof in bladder cancer | |
| CN101836989B (en) | Medicament composition containing tetrandrine, tetrandrine derivatives and histone deacetylase inhibitor and application thereof | |
| Xu et al. | Acetylated xylo-oligosaccharide from Hawthorn kernels inhibits colon cancer cells in vitro and in vivo | |
| US20170340688A1 (en) | Titrated extracts of cynara scolymus and uses thereof | |
| KR102338415B1 (en) | Pharmaceutical composition for preventing or treating osteoarthritis comprising 3,4-dicaffeoylquinic acid | |
| CN113521245B (en) | Pharmaceutical application of reduced glutathione in prevention of pulmonary nodule from increasing malignant transformation | |
| US9458086B1 (en) | Compositions and methods for adipocyte modulation | |
| CN112957357B (en) | Target KLF4 ubiquitination small molecule inhibitor and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20200903 Address after: 518000, block a, building 9, Shenzhen Bay science and technology ecological park, Baishi Road, high tech Zone community, Yuehai street, Nanshan District, Shenzhen City, Guangdong Province Applicant after: Shenzhen Junyuan Biotechnology Co.,Ltd. Address before: Zhongshan Science Park by the road in Liuhe District of Nanjing City, Jiangsu province 211505 building D No. 9 Applicant before: NANJING TUORUIPU GENE TECHNOLOGY Co.,Ltd. |
|
| TA01 | Transfer of patent application right | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |