CN104644622A - Use of chlorogenic acid in preparation of medicine for preventing and treating pulmonary blastoma through P53, PI3K-Akt and MAPK passageways - Google Patents
Use of chlorogenic acid in preparation of medicine for preventing and treating pulmonary blastoma through P53, PI3K-Akt and MAPK passageways Download PDFInfo
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Abstract
The invention discloses use of chlorogenic acid in preparation of a medicine for treating pulmonary blastoma, in particular relates to use of chlorogenic acid in preparation of a medicine for preventing and treating pulmonary blastoma through P53, PI3K-Akt and MAPK passageways, and also discloses a preparation for treating the pulmonary blastoma. The preparation comprises chlorogenic acid and a pharmaceutically acceptable excipient or an auxiliary.
Description
Technical field
The present invention relates to the purposes of chlorogenic acid in the medicine of preparation treatment pulmonary blastoma, be specifically related to chlorogenic acid preparation by the purposes in the medicine of P53, PI3K-Akt and MAPK path prevention and therapy pulmonary blastoma, belong to drug world.
Background technology
Chlorogenic acid (Chlorogenic acid, CGA), have another name called chlorogenic acid, chemistry 3-0-caffeoyl guinic acid (3-0-caffeoylquinic acid) by name, the carboxylic phenolic acid be made up of caffeic acid (Caffeic acid) and quinic acid (Quinic acid).
Chlorogenic acid is the product of plant aerobic respiration metabolism; it is the principle active component in many Chinese crude drugs and fruit and vegetable; there is multiple biological activity, as: cardiovascular protective effect, antioxidation, uvioresistant and radiation resistance, antimutagenic and antitumaous effect, antibacterial action, antivirus action, blood lipid-reducing blood sugar-decreasing effect, immunoregulation effect etc.All have a wide range of applications in the field such as medication chemistry and food.
Pulmonary blastoma is a kind of rare pulmonary primary malignant neoplasm, is divided into adult type pulmonary blastoma and child's pleuropulinonary blastoma.The clinical symptoms of pulmonary blastoma and imaging examination are without specificity, and easy mistaken diagnosis, preoperative diagnosis difficulty, postoperative pathological needs combining form and SABC to consider.The first-selected operative treatment of primary disease, modus operandi adds mediastinal lymphadenectomy art based on lobectomy of lungs.Prognosis and histological type, by stages and tumor locus etc. relevant, overall poor prognosis.
At present, the only resource being used for the treatment of pulmonary blastoma is clinically operation.Primary disease advocates that operation plan is similar to pulmonary carcinoma based on the Comprehensive Treatment of operation, and coordinate mediastinum, hilar lymph node cleaning with the lobe of the lung or full pneumonectomy, adjuvant chemotherapy of patients, the uncertain therapeutic efficacy of radiotherapy is cut, and advocates that postoperation radiotherapy person is very few.This disease is insensitive to chemotherapy, and which kind of chemotherapeutics of application and which kind of chemotherapy regimen are not also come to a conclusion at present.
Summary of the invention
For above-mentioned technical problem, the object of the present invention is to provide a kind of novelty teabag of chlorogenic acid.
Above-mentioned purpose of the present invention is achieved by the following technical solution: the application of a kind of chlorogenic acid in the medicine preparing prevention and therapy pulmonary blastoma.
In the present invention, chlorogenic acid can the generation of Tumor suppression blood vessel, thus treatment pulmonary blastoma and control the transfer of pulmonary blastoma.Chlorogenic acid is the object being reached prevention and therapy pulmonary blastoma by P53, PI3K-Akt and MAPK path.Specifically, chlorogenic acid activates P53 path, promotes the apoptosis of tumor cell and reach the object for the treatment of pulmonary blastoma.In addition, chlorogenic acid is the target spot inhibitor as PI3K and AKT, suppresses PI3K-Akt active, the specifically generation of Tumor suppression blood vessel, thus the transfer for the treatment of pulmonary blastoma and control pulmonary blastoma.In addition, chlorogenic acid is as the kinase whose target spot inhibitor of mapk kinase, suppress mapk kinase kinase activity, thus suppress mapk kinase active, thus suppress MAPK active again, specifically Tumor suppression vascular endothelial cell and tumor vascular generation, thus the transfer for the treatment of pulmonary blastoma and control pulmonary blastoma.
P53 is a tumor suppressor protein, is avoiding playing an important role in the generation of tumor and development, such as, and the apoptosis of tumor cell and the generation etc. of Tumor suppression neovascularity.P53 albumen energy T suppression cell reproductive cycle stays in G
1on the rhythm and pace of moving things point of/S, reach the identification that DNA repairs, to start the reparation of DNA; If DNA unrepairable, then P53 active cell apoptosis program, avoids the continuation merisis of tumor cell.P53 albumen after sudden change may lose the ability being formed with DNA and effectively combine, and stop fissional signal to send.Therefore, damaged cell carries out cell division by uncontrolled, and final formation leads oncogenic development.
Inventor studies discovery, and chlorogenic acid acts on the target gene of the P53 albumen in cell in p53 signal path, activates its target gene, expresses P53 albumen, makes it have biological activity developing with Tumor suppression, play antineoplastic action.PI3K-Akt signal path is as one of signal of interest Signal Transduction Pathways in cell, by affecting the state of activation of downstream wide variety of effector molecules, play the pivotal role promoting cell proliferation and apoptosis inhibit in vivo, the generation of it and kinds of tumors and develop closely related, chlorogenic acid acts on key point p110 α subunit in PI3K-Akt signal path and pAkt or acts on the target gene of these target spots, make these target spots lose original activity or the expression of these target point proteins is suppressed, thus the developing of Tumor suppression, promote that the apoptosis of tumor cell and the leaching of inhibition tumor cell are attacked and shifted.Mitogen activated protein kinase (mitogen-activated protein kinase, MAPK) cascade is the protein serine/threonine superfamily extensively existed in cell, that MAPK can be divided into 4 subtribes: ERK, p38, JNK and ERK5 by cytoplasmic signal transmission to nucleus and the important substance causing nucleus to change.The activation of p38MAPK and ERK, makes cell genetic morphology change, changes spindle shape into by cube, and lowers along with E-cadherin, Promote cell's growth, migration and invasion and attack.JNK plays an important role in the multiple physiology such as cell cycle, production, apoptosis and cellular stress and pathological process.Chlorogenic acid acts on ERK and p38MAPK in MAPK signal path, suppresses the work of ERK and p38MAPK, thus the biology of inhibition tumor cell, migration and invasion.Chlorogenic acid acts on JNK, activates JNK signal path, promotes the apoptosis of tumor cell.
In the present invention, as preferably, described medicine is effective ingredient by chlorogenic acid, adds the preparation that pharmaceutically acceptable adjuvant or complementary composition are prepared from.
Another object of the present invention is to, provide a kind of preparation for the treatment of pulmonary blastoma, described preparation comprises chlorogenic acid and pharmaceutically acceptable excipient or adjuvant.Described adjuvant or excipient include but not limited to mannitol, sodium sulfite, starch, dextrine powder, dehydrated alcohol, water for injection, Icing Sugar, lactose, hypromellose, magnesium stearate, sucrose, PVP K30.
Specifically, preparation of the present invention is oral formulations or ejection preparation.
Wherein, described preparation per unit preparation is containing chlorogenic acid 1-1000mg, and Clinical practice dosage is: 1-100mg/kg.
Beneficial effect of the present invention is that providing a kind of may be used for treating the chlorogenic acid of pulmonary blastoma and the preparation of pharmaceutically acceptable excipient or adjuvant composition.Described medicine has comparatively obvious therapeutic effect to pulmonary blastoma and prognostic is better.
Accompanying drawing explanation
Fig. 1 is the design sketch that chlorogenic acid suppresses pulmonary blastoma hyperplasia.
Fig. 2 is the apoptotic schematic diagram of chlorogenic acid induction pulmonary blastoma.
Fig. 3 is that protein blot experiment detects caspase 3 protein expression schematic diagram.
Fig. 4 is that under various dose concentration, Cell cycle status detects schematic diagram.
Fig. 5 is p53 protein 15 position serine phosphorylation schematic diagram.
Fig. 6 is that pulmonary blastoma apoptosis schematic diagram induced by chlorogenic acid (20mg/ml).
Fig. 7 is the expression of PI3K-Akt path key protein in pulmonary blastoma cell and normal cell (Western Blot result).
Fig. 8 is the dose-effect relationship (p<0.05) that chlorogenic acid affects pulmonary blastoma ability of cell proliferation.
Fig. 9 is that chlorogenic acid affects schematic diagram to pulmonary blastoma cell cycle.
Figure 10 is that chlorogenic acid affects schematic diagram to pulmonary blastoma cell cycle.
Figure 11 is the flow cytometer apoptosis collection of illustrative plates that pulmonary blastoma cell affects by chlorogenic acid.
Figure 12 be chlorogenic acid pulmonary blastoma cell pAkt is expressed affect schematic diagram.
Figure 13 be chlorogenic acid pulmonary blastoma cell pAkt is expressed affect schematic diagram.
Figure 14 is that MTT detects chlorogenic acid and affects schematic diagram to pulmonary blastoma cell proliferation.
Figure 15 is that cell number method detects and greenly formerly affects schematic diagram to pulmonary blastoma cell proliferation.
Figure 16 is that chlorogenic acid (20mg/ml) affects schematic diagram to pulmonary blastoma is apoptotic.
Figure 17 is that chlorogenic acid (20mg/ml) affects schematic diagram to MAPK signal path in pulmonary blastoma cell.
Figure 18 is that chlorogenic acid affects the apoptosis schematic diagram of pulmonary blastoma cell by MAPK signal path.
Detailed description of the invention
Embodiment 1 chlorogenic acid activates P53 embodiment
P53 tumor antioncogene is a transcription factor, plays a crucial role in regulating cell death and various programmed cell.The cell event that p53 participates in regulation and control comprises cell cycle, apoptosis, DNA damage reparation and aging etc.Experiment display chlorogenic acid can induce pulmonary blastoma apoptosis.Pifithrin-α is a species specificity p53 protein inhibitor, and after pifithrin-α process pulmonary blastoma cell, Flow cytometry experiments display pulmonary blastoma apoptosis is completely suppressed.
(1) cell apoptosis assay
Pulmonary blastoma apoptosis is detected with FITC-Annexin V Flow cytometry experiments (BD company apoptosis detection kit).
A. when collecting cell cell in Tissue Culture Flask reaches 60-80% degree of converging, 2mlEDTA-pancreatin is added in Tissue Culture Flask, basis of microscopic observation adds 5ml and entirely cultivates piping and druming termination digestion collecting cell when 90% cell detachment bottle wall, and 200g is centrifugal, and 10mins obtains cell precipitation.Add 5ml culture medium re-suspension liquid, counted under microscope cell.
B. plate is planted by pulmonary blastoma cell 1x10
6individually be inoculated in 100mm Tissue Culture Dish.Tissue Culture Dish is placed in 5%CO
2, cultivate 24 hours in 37 DEG C of incubators.
C. after cell attachment, second day 20mg/ml chlorogenic acid, 100 μMs of pifithrin-α process cells; Matched group DMSO process cell.Tissue Culture Dish is placed in 5%CO
2, cultivate 30mins in 37 DEG C of cell culture incubators by 24 hours.
D. Flow cytometry experiments the 3rd day EDTA-collected by trypsinisation cell, the centrifugal 10mins of 200g, cell PBS liquid washes 2 times; 1x10 is made with 1xBinding buffer is resuspended
6/ ml cell suspension; Be transferred in 5ml streaming pipe by 100 μ L cell suspension, add 5 μ LAnnexin V and 5 μ L Propidium iodide (PI), 15mins is hatched in mixing also room temperature lucifuge; In each streaming pipe, add 4005 μ L 1xBinding buffer, after vortex concussion, flow cytometer detects.
E. experimental result FlowJo software is analyzed.
(2) cell cycle experiment
Process pulmonary blastoma cell after 24,48 and 72 hours with chlorogenic acid (heavy dose of group 40mg/ml, middle dosage group 20mg/ml and low dose group 5mg/ml), Flow cytometry experiments observes periodic state.
A. when collecting cell cell in Tissue Culture Flask reaches 60-80% degree of converging, 2mlEDTA-pancreatin is added in Tissue Culture Flask, basis of microscopic observation adds 5ml and entirely cultivates piping and druming termination digestion collecting cell when 90% cell detachment bottle wall, and 200g is centrifugal, and 10mins obtains cell precipitation.Add 5ml culture medium re-suspension liquid, counted under microscope cell.
B. plate is planted by pulmonary blastoma cell 1x10
6individually be inoculated in 100mm Tissue Culture Dish.Tissue Culture Dish is placed in 5%CO
2, cultivate 24 hours in 37 DEG C of incubators.
C. after cell attachment, second day 40mg/ml, 20mg/ml and 5mg/ml chlorogenic acid; Matched group DMSO process cell.Tissue Culture Dish is placed in 5%CO
2, cultivate 24,48 and 72 hours in 37 DEG C of cell culture incubators.
D. the Flow cytometry experiments incubation time EDTA-collected by trypsinisation cell of specifying, washes cell 3 times with PBS liquid; With 1ml buffer re-suspended cell, vortex concussion adds 4ml 70% pre-cooled ethanol simultaneously, fixes more than 12 hours for 4 DEG C; PBS liquid washes 3 times, adds 400 μ LPBS buffer re-suspended cells, and add PI and RNaseA to final concentration 50 μ g/ml, room temperature lucifuge uses cells were tested by flow cytometry Cell cycle status after hatching 30mins.
E. experimental result FlowJo software is analyzed.
(3) experimental result
A. chlorogenic acid is first detected on the impact of pulmonary blastoma hyperplasia.MTT experiment finds, during chlorogenic acid low dose group 5mg/ml, and pulmonary blastoma cell and suppressed; In chlorogenic acid during dosage group 20mg/ml, pulmonary blastoma cell is subject to significant suppression (p<0.05) (Fig. 1).
In Fig. 1, experimental result is the accumulative of 3 independent MTT experiment data statisticss, and each dosage of chlorogenic acid is high in an experiment 16 repeating holes, and experimental result repeatability is high.
B. chlorogenic acid is by the hyperplasia of apoptosis-induced suppression pulmonary blastoma.It is that the apoptotic result of pulmonary blastoma directly induced by chlorogenic acid that pulmonary blastoma hyperplasia reduces.Flow cytometry experiments result shows, after processing cell with low dosage chlorogenic acid (5mg/ml), cell surface increases in conjunction with AnnexinV and PI dyeing, and after adding chlorogenic acid, can observe FITC-AnnexinV and PI positive cell as far back as 30 minutes increases (Fig. 2).Protein blot experiment confirms, with the chlorogenic acid process pulmonary blastoma cell of 20mg/ml after 24,48 and 72 hours, cracking caspase3 protein expression increases (Fig. 3).Manage pulmonary blastoma cell after 24,48 and 72 hours with the green original place of various dose concentration, with PI, cell is dyeed, then change (Fig. 4) with flow cytomery Cell cycle status.
C. chlorogenic acid activates p53 signal path.P53 tumor antioncogene is a transcription factor, plays a key role in regulating cell death and various programmed cell.The cell event that p53 participates in regulation and control comprises cell cycle, apoptosis, DNA damage reparation and aging etc.Experiment display, chlorogenic acid can induce pulmonary blastoma apoptosis.Meanwhile, protein blot experiment shows, and after chlorogenic acid (20mg/ml) processes pulmonary blastoma cell, p53 protein 15 position serine phosphorylation increases sharply (Fig. 5), illustrates that p53 is activated.
Pifithrin-α is a species specificity p53 protein inhibitor.After pifithrin-α pretreatment pulmonary blastoma cell, Flow cytometry experiments display chlorogenic acid (20mg/ml) induces pulmonary blastoma apoptosis completely suppressed (Fig. 6).In matched group, cell FITC-AnnexinV stained positive rate is 11%; Chlorogenic acid processed group cell FITC-AnnexinV stained positive rate is; In pifithrin-α group, cell FITC-AnnexinV stained positive rate is 10%.Cell apoptosis assay proves further, and chlorogenic acid induction pulmonary blastoma apoptosis is by activating p53 signal path.
Embodiment 2 chlorogenic acid suppresses PI3K-Akt activity Example
PI3K-Akt is one of most important signal transduction pathways of cell biological function such as cell proliferation, apoptosis and cell cycle, and the generation of its abnormal activation and malignant tumor develops closely related.Chlorogenic acid effectively can block the corresponding molecular target on pulmonary blastoma cell PI3K-Akt signal path, suppress the growing multiplication of pulmonary blastoma cell, inducing cell cycle arrest, promotes apoptosis, and significantly lowers expression and the activation of signal path downstream signaling proteins matter.
(1) experimental technique
Pulmonary blastoma cell culture, in containing in the DMEM culture fluid of 10% calf serum, adds the penicillin of 100IU/L and the streptomycin of 100mg/L, is placed in 37 DEG C, 5%CO
2constant incubator in cellar culture, after at the bottom of cell covers with bottle, discard culture fluid, PBS liquid rinses twice, then digests 5 minutes with the pancreatin of 0.25% and the EDTA of 0.02%, then sub-bottle is cultivated, and within 2 to 3 days, goes down to posterity once, and trophophase cell of taking the logarithm is for testing.
A.PI3K-Akt pathway activity detects
The pulmonary blastoma cell of trophophase of taking the logarithm is inoculated in six well culture plates after trypsinization, is placed in 5%CO
2incubator, 37 DEG C of cultivations, in time growing to 80% Fusion Strain, collecting cell extracts total protein, measures protein concentration by BCA method.The expression of PI3K (p110 alpha subunit) and pAkt (S473, T308) in cell is detected by Western Blot method.
B. cell cycle and apoptosis analysis
To the pulmonary blastoma cell of exponential phase be in, by 1 ~ 5x10
4cells/well density is inoculated in six orifice plates.Cultivate after 24 hours, add chlorogenic acid (5,20 and 40mg/ml) respectively and act on 24 hours, remove cell culture fluid, wash cell once with ice PBS.Add trypsinization, collecting cell, adopt the mono-dye of PI (apoptosis detects and adopts the two dye method of FITC-AnnexinV and PI), carry out cell cycle and apoptosis detection respectively with flow cytometer.Each identical experiment repeats 3 times.
C. chlorogenic acid affects pulmonary blastoma cell PI3K-Akt pathway activity
To the pulmonary blastoma cell of exponential phase be in, by 1 ~ 5x10
4cells/well density is inoculated in six orifice plates.Cultivate after 24 hours, add chlorogenic acid (5,10,15 and 20mg/ml) respectively and act on 48 hours, collecting cell, extract total protein.The expression of PI3K (p110 alpha subunit) and pAkt (S473, T308) in cell is detected by Western Blot method.
D. statistical analysis
Adopt SPSS11.5 software to carry out data statistic analysis, all data are expressed as mean+/-standard error (Means ± SEM).
(2) result
The expression Western Blot of a.PI3K-Akt path key protein in normal cell and pulmonary blastoma cell analyzes and finds, the expression of the key protein PI3K (p110 alpha subunit) in PI3K-Akt path in pulmonary blastoma cell and normal cell is without significant difference; Total pAkt albumen change expression no significant difference; The expression compared with normal cell of pAkt (S473, T308) in pulmonary blastoma significantly raises (p<0.05) (Fig. 7).
Chlorogenic acid to the display of pulmonary blastoma cell inhibitory effect effect MTT colorimetric determination result, chlorogenic acid in dose-effect relationship (5,10,15 and 20mg/ml) growth (p<0.05) (Fig. 8) in dose-dependent suppression pulmonary blastoma cell.
C. the affect flow cytometer cell cycle testing result of chlorogenic acid on the change of pulmonary blastoma cell cycle and apoptosis rate shows, after chlorogenic acid (20mg/ml) acts on 24 hours, there is obvious G0/G1 phase some retardation in pulmonary blastoma cell, the cell proportion being in the S phase accordingly significantly reduces (p<0.05) (Fig. 9, Figure 10) compared with matched group.
Flow cytometer apoptosis laboratory test results shows, and chlorogenic acid effect pulmonary blastoma cell is after 24 hours, and pulmonary blastoma apoptosis rate significantly raises (p<0.05) (Figure 11, table 1) compared with matched group.
Table 1. each dosage group process pulmonary blastoma apoptosis rate
| Grouping | Pulmonary blastoma cell (%) |
| Matched group | 10.2±2.7 |
| Chlorogenic acid (5mg/ml) | 20.3±3.5** |
| Chlorogenic acid (10mg/ml) | 30.1±8.5** |
| Chlorogenic acid (15mg/ml) | 38.9±9.2** |
| Chlorogenic acid (20mg/ml) | 49.6±12.6** |
*: compared with matched group, p<0.05.
D. the affect Western Blot result of chlorogenic acid on pulmonary blastoma cell Akt activity shows, pulmonary blastoma cell after chlorogenic acid (20mg/ml) hatches 48 hours, the expression compared with matched group remarkable reduction (p<0.05) (Figure 12, Figure 13) of pAkt (T308 with S473).
Embodiment 3 chlorogenic acid suppresses MAPK signal path activity Example
(1) process pulmonary blastoma cell different time respectively with the chlorogenic acid of 5,10,15 and 20mg/ml tetra-kinds of dose concentrations, detect the proliferative conditions (Figure 14, Figure 15) of cell.
Flow cytomery finds, the chlorogenic acid of 20mg/mg acted on pulmonary blastoma cell after 24 hours, compared with normal control group, reality figure occurs typicality cell hypodiploid apoptotic peak, apoptosis rate is 39.59%, apparently higher than the apoptosis rate 1.89% (table 2, Figure 16) of matched group.
Table 2. chlorogenic acid is on the apoptotic impact of pulmonary blastoma (n=15, means ± SEM)
Note: compare with Normal group, * p<0.05.
(2) for proving the apoptotic signal path of green former induction pulmonary blastoma, the pulmonary blastoma cell cultivated with chlorogenic acid process, three Major Members in observation signal path, the i.e. change of ERK1/2, JNK and p38MAPK.The phosphorylation level change of three signal transducers is detected with Western Blot.Result shows, and when 20mg/ml chlorogenic acid acted on pulmonary blastoma cell after 24 hours, starts to raise, within 48 hours, obviously raises.Obviously reduce after ERK and p38MAPK48 hour, see Figure 17.Show green former be JNK by activating in pulmonary blastoma cell in MAPK path, suppress ERK and p38MAPK to control the proliferation and apoptosis of pulmonary blastoma cell.
Apoptosis-related for proving that chlorogenic acid activates JNK, suppression ERK and p38MAPK signal path and pulmonary blastoma, by the apoptosis situation using flow cytomery cell after the inhibitor PD98059 process cell of signal path.As shown in figure 18, after blocking ERK and p38MAPK signal path, apoptosis rate rises (Figure 18 C) further compared with under simple chlorogenic acid inductive condition.Above result shows that JNK, ERK and p38MAPK take part in chlorogenic acid induction pulmonary blastoma apoptosis.
Embodiment 4 chlorogenic acid prevention and therapy pulmonary blastoma embodiment
Mouse lung blastoma model, selects C57BL/6 mice, male, 18-20g.During experiment, get well-grown tumor tissues, make tumor cell suspension with physiological saline solution by after 1:3 dilution proportion, every mice axil back inoculation 0.2ml tumor liquid.Inoculation animal random packet rear next day, weighs, and starts administration.Solvent control group injects 0.2ml administration by every 10g mouse peritoneal, every day 1 time.Chlorogenic acid injection administration volume is every 10g mouse peritoneal injection 0.2ml, every day 1 time, successive administration 13 days.
Laboratory animal is divided into 7 groups, negative control group, solvent control group, chlorogenic acid 5mg/kg, 10mg/kg, 20mg/kg tri-dosage groups.Often organize 15 animals.After chlorogenic acid drug withdrawal, next day puts to death animal, weighs, and stripping tumor also claims tumor weight.Tumor control rate (%) is calculated according to tumor weight.Body weight and tumor are reused means standard deviation (x ± SD) and are represented, and carry out between each administration group and negative control group.
Injection gives the growth inhibited effect that chlorogenic acid for injection is obvious dose dependent to mouse lung blastoma.(table 3).
Table 3. chlorogenic acid is to the blastomatous antitumor action of mouse lung
Note: * * * P<0.001, compares with negative control group.
Claims (10)
1. the application of chlorogenic acid in the medicine preparing prevention and therapy pulmonary blastoma.
2. apply as claimed in claim 1, described medicine is that chlorogenic acid is by P53, PI3K-Akt and MAPK path prevention and therapy pulmonary blastoma.
3. apply as claimed in claim 2, described medicine is that chlorogenic acid activates P53 path, promotes the apoptosis of tumor cell and reaches treatment pulmonary blastoma.
4. apply as claimed in claim 2 or claim 3, described medicine is the target spot inhibitor of chlorogenic acid as PI3K and AKT, suppress PI3K-Akt active, preferred described medicine is the generation of chlorogenic acid Tumor suppression blood vessel, thus the transfer for the treatment of pulmonary blastoma and control pulmonary blastoma.
5. the application as described in any one of claim 2-4, described medicine be chlorogenic acid as the kinase whose target spot inhibitor of mapk kinase, suppress mapk kinase kinase activity, thus suppress mapk kinase active, thus suppress MAPK active again.
6. apply as claimed in claim 5, described medicine is chlorogenic acid Tumor suppression vascular endothelial cell and tumor vascular generation, thus the transfer for the treatment of pulmonary blastoma and control pulmonary blastoma.
7. the application as described in any one of claim 1-6, described medicine comprises with chlorogenic acid and pharmaceutically acceptable adjuvant or complementary composition.
8. be used for the treatment of a medicine for treatment pulmonary blastoma, comprise chlorogenic acid and pharmaceutically acceptable adjuvant and/or excipient.
9. medicine as claimed in claim 8, described medicine is ejection preparation or oral agents.
10. medicine as claimed in claim 8 or 9, described drug use dosage is 1-100mg/kg.
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| PCT/CN2016/072126 WO2016127789A1 (en) | 2015-02-13 | 2016-01-26 | Application of chlorogenic acid in preparing medicines for preventing and treating pulmonary blastoma by using p53, pi3k-akt, and mapk paths |
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| WO2016127789A1 (en) * | 2015-02-13 | 2016-08-18 | 四川九章生物科技有限公司 | Application of chlorogenic acid in preparing medicines for preventing and treating pulmonary blastoma by using p53, pi3k-akt, and mapk paths |
| CN107412736A (en) * | 2017-08-08 | 2017-12-01 | 四川九章生物科技有限公司 | A kind of antineoplastic combination medicine and its purposes in cancer therapy drug is prepared |
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| WO2016127789A1 (en) * | 2015-02-13 | 2016-08-18 | 四川九章生物科技有限公司 | Application of chlorogenic acid in preparing medicines for preventing and treating pulmonary blastoma by using p53, pi3k-akt, and mapk paths |
| CN107412736A (en) * | 2017-08-08 | 2017-12-01 | 四川九章生物科技有限公司 | A kind of antineoplastic combination medicine and its purposes in cancer therapy drug is prepared |
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