CN104800217A - Application of Chinese medicine monomer (lycorine) to preparation of drugs for treating prostate tumors - Google Patents
Application of Chinese medicine monomer (lycorine) to preparation of drugs for treating prostate tumors Download PDFInfo
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Abstract
The invention discloses application of a Chinese herbal medicine micro-molecule monomer compound (lycorine) to preparation of potential drugs for treating prostate tumors and related diseases. The invention further discloses a prostate cancer resistance molecular mechanism of the Chinese herbal medicine micro-molecule monomer compound.
Description
Technical field
The present invention relates to medical art, be specifically related to the application that Chinese herbal medicine monomer lycorine is used as in preparation to treat in the potential drug of prostate apoptosis response-4.
Background technology
With regard to world wide, carcinoma of prostate is the number one killer in global elderly men malignant tumor, all occupies the prostatitis of all cancer species at its sickness rate of western developed country and fatality rate; In China, carcinoma of prostate in recent years also with annual 10% speed sharp increase, especially China just steps into aging society, and Future Ten year probably occurs onset peak.Carcinoma of prostate due to its crypticity anatomically, one after diagnosing great majority be middle and advanced stage thus lost radical treatment chance.Early prostate cancer generally carries out radical treatment by operations such as Testectomies, if carcinoma of prostate proceeds to middle and advanced stage, generally be difficult to radical cure, can only based on endocrine therapy (being also androgen deprivation therapy), although this therapy has certain curative effect, but generally only can maintain 1.5-4 to the control of tumor, can further develop subsequently becomes castration-resistant prostate cancer, and to other organ metastasis beyond prostate.Transitivity castration-resistant prostate cancer is the difficult point in prostate cancer therapy field always.
In the treatment means of carcinoma of prostate, chemical medicinal treatment occupies critical role.But, although chemotherapeutics new in recent years constantly occurs, chemotherapy regimen is updated, antiprostate cancer is ubiquity target-oriented drug difference and the problem such as toxic and side effects is stronger still, limit performance and the life-time service of curative effect of medication, and the multidrug resistance that carcinoma of prostate shows is the main cause of tumor recurrence, transfer and even Endodontic failure always, this is also the most common and the most formidable problem of clinical prostate cancer treatment.Current conventional chemotherapeutics is not very good to the curative effect of carcinoma of prostate, and this makes to find active component from natural materials, becomes the important development strategy of exploitation antiprostate cancer.Medicinal herb components is the main source of modern medicine medication, 70% all to be extracted by the antitumor drug of U.S. FDA approval listing or is derived from natural plants, illustrates that the exploitation of conventional medicament is feasible and has obtained successful scheme in modern medicine.The resources of medicinal plant of China is enriched, and excavates the effective monomer with anti-prostate cancer activity and have broad prospect of application from Chinese traditional herbs in the new drug development of carcinoma of prostate.
Summary of the invention
The Chinese herbal medicine monomer that the object of the invention is to disclose a kind of lycorine by name can be used as the compound of being treated tumor of prostate by suppression JAK/STAT3 signal path, comprises its acceptable salts, solvated compounds (hydrate) and Chinese patent medicine compound recipe etc.
Chinese medicine monomer lycorine (Lycorine also can be abbreviated as Lyc) is a kind of isoquinoline alkaloid be separated from a kind of perennial herb medicinal plants Bulbus Lycoridis Radiatae bulb that China extensively distributes.Medical science shows that lycorine has the multiple excellent pharmacologically actives such as analgesia, antipyretic, antiinflammatory, sterilization, antiviral, blood pressure lowering, malaria, leukemia in recent years, and it has the representative Fourth Ring skeleton that a large class Bulbus Lycoridis Radiatae alkaline alkaloid all contains, in addition its good biological safety, therefore, the synthesis of lycorine and activity research have attracted the research interest of numerous synthetic organic chemist and biologist, pharmaceutical chemistry and biological study all have far-reaching medical research and is worth.
The present invention proposes the application in the medicine of preparation treatment prostate cancer disease of a kind of Chinese herbal medicine monomer micromolecular compound lycorine or its hydrate or pharmaceutically acceptable salt, and described lycorine has with following formula (I) structure:
Wherein, described medicine comprises the medicine for the treatment of carcinoma of prostate malignant tumor.
Wherein, described medicine be used alone or with other drug conbined usage.
Wherein, described medicine is formulated into injectable fluid, aerosol, emulsifiable paste, gel, pill, capsule, syrup, transdermal patch or excipient.
The invention allows for the application of a kind of monomer micromolecular compound formula (I) lycorine in the medicine of preparation treatment carcinoma of prostate malignant tumor.
The invention allows for a kind of method that monomer micromolecular compound formula (I) lycorine is applied to treatment prostate cancer disease.Described method comprises: by containing monomer micromolecular compound formula (I) lycorine or its hydrate or pharmaceutically acceptable salt or containing its medicament by suitable administering mode comprise oral, intravenous injection, intramuscular injection, subcutaneous injection, sublingual administration, rectal perfusion, eye drip, nasal spray, mouthspray, also can through skin surface locally or the mode of whole body transdermal administration apply.
The invention allows for a kind of Chinese herbal medicine monomer micromolecular compound formula (I) lycorine or its hydrate or pharmaceutically acceptable salt and suppress the application in prostate cancer tumor cells propagation, growth, migration, infiltration.
The invention allows for a kind of monomer micromolecular compound formula (I) lycorine and be applied to the method suppressing prostate cancer tumor cells propagation, growth, migration, infiltration.Described method comprises MTS experiment and detects tumor cell proliferation speed, colony formation detects growth of tumour cell ability, cut (Wound-healing) experiment detects tumor cell lateral transfer ability, Transwell experiment detects the ability of tumor cell vertical migration and infiltration, (EMT) character mutation is transformed by the change-detection tumor cell Epithelial and stromal of observation of cell morphological characteristic, in nude mouse, subcutaneous tumor-bearing model detects tumor growth ability, in nude mouse, prostate original position tumor-bearing model detects tumor growth and transfer ability.
The invention allows for a kind of pharmaceutical composition, it contains such as formula the lycorine shown in (I) or its hydrate or pharmaceutically acceptable salt, and pharmaceutically acceptable carrier.
Wherein, described pharmaceutical composition is formulated into injectable fluid, aerosol, emulsifiable paste, gel, pill, capsule, syrup, transdermal patch or excipient.
In a specific embodiments of the present invention, this Chinese herbal medicine single-body type (I) lycorine just can the growth in vitro of strong inhibition Prostatic cancer cell lines and migration in lower concentration (5-10 μM).In a specific embodiments of the present invention, in mouse model, this monomer administration of 10mg/kg/day can effectively suppress prostate gland cancer cell tumor growth and transfer.In a specific embodiments of the present invention, this single-body type (I) lycorine is mainly through suppressing JAK/STAT3 signal path to play the function of anti-prostate cancer.
Although lycorine has above-mentioned numerous excellent biologic activity, it treatment solid tumor in function also not studies have reported that.The present invention by literature survey widely, screens Chinese herbal medicine monomer lycorine at first, follow-up in external, body and the many levels such as biochemical molecular level inquire into the anti-tumor activity of lycorine.Experiment shows, Chinese medicine monomer lycorine can suppress the propagation of multiple castration-resistant prostate cancer cell strain, cell death inducing, block the migration of prostate gland cancer cell and invasion and attack and reverse the epithelial-mesenchymal cell transformation (epithelial mesenchymal transitions, EMT) of carcinoma of prostate; In vivo, lycorine can suppress the growth of prostate cancer xenograft tumor and transfer and extend tumor-bearing mice life cycle; Further experiment discloses lycorine and realizes its biological mechanism suppressing prostate cancer growth and transfer by downward intracellular signaling and activating transcription factor 3 (signal transducer and activator oftranscription 3, STAT3) signal path.
Accompanying drawing explanation
Figure 1 shows that lycorine suppresses propagation, the migration and invasion of prostate gland cancer cell.
Figure 2 shows that lycorine suppresses the growth in vitro of prostate gland cancer cell by cell death inducing.
Figure 3 shows that the inhibitory action of lycorine to Prostate Carcinoma of Mice subcutaneous lotus tumor growth model.
Figure 4 shows that lycorine is to the inhibitory action in the growth of Prostate Carcinoma of Mice original position lotus tumor and metastasis model.
Figure 5 shows that lycorine reverses the EMT of prostate gland cancer cell EGF induction, its anti-prostate cancer activity relies on STAT3 and expresses.
Figure 6 shows that lycorine suppresses the STAT3 transcriptional activity of prostate gland cancer cell.
Detailed description of the invention
In conjunction with following specific embodiments and the drawings, the present invention is described in further detail, and protection content of the present invention is not limited to following examples.Under the spirit and scope not deviating from inventive concept, the change that those skilled in the art can expect and advantage are all included in the present invention, and are protection domain with appending claims.Implement process of the present invention, condition, reagent, experimental technique etc., except the following content mentioned specially, be universal knowledege and the common practise of this area, the present invention is not particularly limited content.
Embodiment one: lycorine suppresses propagation, the migration and invasion of prostate gland cancer cell
Technical method
1, cell culture and cell survival experiment
Prostate gland cancer cell PC-3M used in the present invention, LNCaP, 22RV1 and DU145 are purchased from ATCC cell bank, and people's normal prostatic epithelium cell strain PNT1A is from Shanghai Communications University.Cell culture is in 37 DEG C of constant incubator (humidity 95%, CO
2concentration 5%) in, culture medium is the RPMI1640 containing 10% hyclone.Cell survival is measured by MTS method.Prostate cell strain PC-3M, LNCaP, 22RV1 and DU145 and people's normal prostatic epithelium cell strain PNT1A are with 5x10
3individual/hole density is seeded to 96 orifice plates, adds this monomeric compound of variable concentrations after 24h, and matched group adds the DMSO of equivalent, establishes 3 multiple holes for each group.After continuing to cultivate 24h, 48h, 72h and 96h respectively, add 20 μ lMTS and hatch 1-4 hour in 37 DEG C, detect the absorbance at 490nm place by microplate reader.Experiment is independent to be repeated 3 times.Cell survival rate (%)=add medicine OD value/matched group OD value * 100%.
2, line migration experiment
PC-3M cell is seeded to 6 orifice plates, at 37 DEG C, 5%CO
2cellar culture 24h in incubator, grows to 100% completely to cell.Change serum-free medium, continue hungry cultivation 12h.In the culture hole covering with cell, rule with the sterilizing pipettor gun head of 10 μ l, wash cell twice with PBS after line, the cell floated is washed away.Respectively to adding this monomeric compound of variable concentrations in cell culture well, matched group adds the DMSO of equivalent, and 37 DEG C are continued cellar culture 12h.Basis of microscopic observation cell thinks the situation that dashed part moves, and takes pictures.The migration of statistical analysis various dose medicine group enters the cell quantity of scribe area, determines the impact of medicine on cell migration ability.
3, Transwell cell migration Matrigel
Digest and count the PC-3M cell being in exponential phase, cell is resuspended in serum-free and is dissolved with in the basal medium of this monomeric compound of variable concentrations, and cell is with 5x10
4(200 μ L) is seeded in the upper room of Transwell cell in individual/hole, and matched group adds the DMSO of equivalent.The complete medium that 600 μ L contain this monomeric compound of corresponding concentration is then added in lower room.Be placed in cell culture incubator and cultivate 12h to 18h.Take out Transwell cell paraformaldehyde and fix little ventricular cell, after fixing 20min.2 ‰ crystal violet dye liquors are by cell dyeing process 5min, and cleaning cell, washes off unconjugated crystal violet, with the upside of cotton swab wiping Transwell cell gently, wiped by the cell not moving to downside.Natural drying, takes pictures under microscope, adds up the cell number in multiple visual field.Cell invasion experiment need in advance at cell barrier film upper berth one deck matrigel.Cell migration rate (%)=add medicine cell migration number/cellular control unit transport number * 100%.
Experimental result
Cell proliferation experiment result shows lycorine in prostate gland cancer cell with the mode antiproliferative effect of dose dependent, its IC50 is between 5 μMs to 10 μMs, and the propagation of lycorine to people's normal prostatic epithelium cell strain PNT1A only has slight influence (Figure 1B), abscissa represents lycorine concentration.This inhibit activities of lycorine has also showed time dependence (Fig. 1 C) simultaneously.Neoplasm metastasis and invasion and attack are important steps of tumor development.Our experimental result shows the lateral transfer (Fig. 1 D), vertical migration (Fig. 1 E) and the invasion and attack (Fig. 1 F) that to suppress prostate gland cancer cell PC-3M during lycorine can be tested in vitro in the mode of dose dependent.
Embodiment two: lycorine suppresses the growth in vitro of prostate gland cancer cell by cell death inducing
Technical method
1, colony formation
Digestion process is in the corresponding cell of exponential phase, and counts, every hole 1x10
3individual cell is inoculated in six orifice plates, guarantees that the cell distribution inoculated is even.After cell attachment, change liquid add complete medium containing this monomeric compound of corresponding concentration.After cultivating one week, original culture medium is sopped up with sucking pump, phosphate buffer cleans 3 times, with paraformaldehyde solution, process (20min) is fixed to cell, then 2 ‰ crystal violet dye liquors are by cell dyeing 5min, finally clean gently with the tap water of sluggish flow, to wash unconjugated crystal violet dye liquor off, natural drying at room temperature.Take pictures under microscope, calculate cell clonal formation quantity.
2, live/dead cell dyeing (Live/dead staining assay) experiment
The PC-3M cell that digestion growth conditions is good, in 96 orifice plates, every hole adds 5 × 10
3individual cell.After cell attachment, add the complete medium containing this monomeric compound of corresponding concentration in hole, each concentration repeats three holes.96 orifice plates are put back in cell culture incubator and are continued to cultivate.After 36h, 0.5 μ l EthD-1 and 2 μ l Calcein AM is dissolved in 1ml PBS, adds in 96 orifice plates with the amount in 20 μ l/ holes.After room temperature lucifuge hatches 30 minutes, 96 orifice plates Taking Pictures recording cell under fluorescence microscope sends the situation of HONGGUANG and green glow, and redness is dead cell, and green is living cells.Calculate cell quantity, statistics cell mortality.Cell mortality (%)=dead cell number/total cellular score * 100%
3, apoptosis (Apoptosis) experiment
PC-3M cell is inoculated in 6 orifice plates, within 24 hours, after cell attachment, adds the complete medium containing this monomeric compound of corresponding concentration, after 24 hours, utilizes apoptosis detection kit to carry out apoptosis detection.When fluidic cell apoptosis detects, cell is divided into and does not contaminate group, single dye PI group, single dye Annexin V group and the two dye group of PI, Annexin V.Collect culture medium supernatant, 1mLPBS reclaims after washing cell.Peptic cell, after stopping digestion, collecting cell is in the centrifuge tube of correspondence, centrifugal.With Milli-Q water, 10 × Binding Buffer is diluted to 1 × solution.Cell PBS after centrifugal washes 2 times, recentrifuge.After exhaustion PBS, often pipe add 100 μ L be diluted to 1 × binding buffer liquid, blow and beat gently with liquid-transfering gun, make cell resuspended, do not contaminate group and do not add PI and Annexin V, single dye PI group adds PI 5 μ L, and single dye Annexin V group adds Annexin V 5 μ L, the two dye group of Annexin-V-PI all adds each 5 μ L of PI and Annexin V, mixing.Room temperature lucifuge hatches 15 minutes, is transferred to by cell in 5mL streaming pipe, machine testing on flow cytometer.After flow cytomery, have 4 quadrants in the image drawn, different quadrant represents different cell population, and wherein left upper quadrant, left lower quadrant, right upper quadrant, right lower quadrant represent dead cell respectively, normal non-apoptotic cell, non-viable apoptotic cell and viable apoptotic cell.
4, immunoblotting (Western Blot) experiment
Cell is with after 10ng/ml EGF and variable concentrations drug treating 48h, albumen is extracted through lysate cell lysis, through the protein example of polyacrylamide gel PAGE electrophoretic separation after denatured by boiling, transfer on cellulose nitrate film, hatch with corresponding protein antibody, hatch with two antibody of fluorescent labelling again, then with the expression sweeping film instrument Odyssey and detect this albumen.
Experimental result
Colony formation found that the lycorine of 5 μMs significantly can suppress PC-3M, the Clone formation (Fig. 2 A) of LNCaP, 22RV1 and DU145 tetra-kinds of prostate gland cancer cells.As the live/dead cell dyeing experiment of evaluation and test lycorine to prostate gland cancer cell toxicity, its result demonstrates the death (Fig. 2 B) that lycorine can aggravate PC-3M.In addition, lycorine dose-dependently can also induce the apoptosis of PC-3M cell, when the lycorine concentration added increases to 50 μMs from 0 μM, the cell concentration of apoptosis increases to 54.08% (Fig. 2 C) from 10.04%, Fig. 2 D is shown in the statistical result of PC-3M, DU145, LNCaP apoptosis.Meanwhile, Western Blot tests discovery, and the expression of apoptosis marker protein CL-PARP and CL-caspase-3 raises (Fig. 2 E) with the increase of lycorine concentration.Above experimental result shows, lycorine is the growth in vitro being suppressed prostate gland cancer cell by cell death inducing.
Embodiment three: lycorine is to the inhibitory action of Prostate Carcinoma of Mice subcutaneous lotus tumor growth model
Technical method
By 1 × 10
6individual Human Prostate Cancer Cells PC-3M is subcutaneously injected into immunodeficient mouse (BLAB/c-nude, nude mice) dorsal sc, treats that Subcutaneous tumor grows to 100mm
3during left and right, mice is divided into three groups (often organizing 10).Low dose group mice lumbar injection every day 5mg/kg is dissolved in the lycorine of DMSO, high dose group mice lumbar injection every day 10mg/kg is dissolved in the lycorine of DMSO, matched group injection equal-volume DMSO, within every 2 days, measure and record the length of Mouse Weight and tumor and wide, continuous dispenser put to death mice after 18 days.Get Subcutaneous tumor, take pictures.According to formula volume=length × wide
2× 0.52 calculates, statistics gross tumor volume.
Experimental result
Prostate gland cancer cell subcutaneous lotus tumor experimental result finds that no matter high dose or the lycorine of low dosage all can the growths of effective Tumor suppression, and present dose dependent, the effect more remarkable (Fig. 3 A and Fig. 3 B) of the lycorine dosage Tumor suppression growth of 10mg/kg/day.
Embodiment four: lycorine is to the inhibitory action in the growth of Prostate Carcinoma of Mice original position lotus tumor and metastasis model
Technical method
In metastatic prostate cancer cell PC-3M, proceed to LUC Photinus pyralis LUC Photinus pyralis FL (Luciferase) structure surely turn cell line, this cell that surely turns can expressing luciferase, can fluorescence be sent after luciferase contacts with its substrate luciferin, quantity and the position of cell can be detected by living animal imaging system.Build after surely turning cell line, the mixing of cell matrigel is expelled to mouse prostate dorsal part leaf, PC-3M Growth of Cells in Mice Body and transfer case just can be detected by bioluminescence imaging technology.By 5 × 10
5individual PC-3M-luc cell infusion, to immunodeficient mouse prostate dorsal part leaf, detects luciferase expression with living imaging system Xenogen IVIS 2000 Luminal Imager in 7 days afterwards.Mice is divided into three groups (often organizing 20), low dose group mice lumbar injection every day 5mg/kg is dissolved in the lycorine of DMSO, high dose group mice lumbar injection every day 10mg/kg is dissolved in the lycorine of DMSO, matched group injection equal-volume DMSO, within every 5 days, detect and record data, within every 2 days, measure Mouse Weight, continuous dispenser put to death mice after 30 days.Peel off tumor, take pictures, carry out H & E and dye and immunohistochemical experiment, and dissect out typical transitivity target organ liver, lung, kidney, spleen and bone and prostate and lymph node, detect neoplasm metastasis situation.
Experimental result:
As illustrated in figures 3 c and 3d, be medication therapeutic effect figure to mouse prostate cancer in situ after 30 days, taken pictures by living animal imaging system.Due in tumor cell with luciferase, by squeeze into fluorescein substrate in Mice Body after, tumor cell can send fluorescence, utilizes living animal imaging system can determine position and the size of tumor cell.In figure, shade represents fluorescence signal, and show that this region has tumor cell to assemble, it is larger that fluorescence intensity more deeply feels bright tumor.The experimental result display lycorine dosage of 5mg/kg/day and the transfer of lycorine dosage to prostate carcinoma in-situ of 10mg/kg/day all have inhibitory action, and the lycorine dosage of 10mg/kg/day suppresses the transfer effect of prostate carcinoma in-situ more remarkable.The mice tumor in situ that administration is peeled off for 30 days afterwards, the tumor of 10mg/kg/day dosed administration group is significantly less than matched group (Fig. 3 E).Mouse survival curve during Fig. 3 F is administration, during this period, matched group has 6 dead mouses, dead 4 mices of lycorine dosing group of 5mg/kg/day, and the lycorine dosing group of 10mg/kg/day only has 2 dead mouses.Finding the analysis of prostate gland cancer cell after medication to each target organ transfer case, almost there is not target organ transfer (Fig. 4 A and Fig. 4 B) of tumor cell in the lycorine administration group of 10mg/kg/day.H & E dyes and ImmunohistochemistryResults Results and statistic analysis result show, 10mg/kg/day dosed administration group is compared with matched group, the expression of E-cadherin and CL-caspase 3 increases, p-STAT3 and Ki-67 expression reduces, show that lycorine may inhibit STAT3 signal path, and with reverse epithelial cell mesenchymal transformation relevant (Fig. 4 C and Fig. 4 D).Above data all show, lycorine effectively can suppress growth and the transfer of tumor of prostate.
Embodiment five: lycorine reverses the EMT of prostate gland cancer cell EGF induction
Technical method
Polymerase chain reaction (PolymeraseChainReaction, PCR) test: cell is with after 10ng/ml EGF and variable concentrations drug treating 48h, with TRIzol separation and Extraction RNA, after reverse transcription, detect its mRNA level in-site with corresponding gene Auele Specific Primer by real-time quantitative PCR (RT-PCR).
Experimental result
After PC-3M is induced by EGF, cell becomes multipolarization, out-of-shape, is the Interstitial cell form of many feelers from the epithelial cell Morphological Transitions that marshalling is level and smooth.Epithelial cell marker protein E-cadherin expresses reduction, mesenchymal cell marker protein N-cadherin, vimentin, fibronectin express and raise (Fig. 5 C).Lycorine can reduce N-cadherin in concentration dependant ground, vimentin, fibronectin express and correspondingly raise E-cadherin and express (Fig. 5 C), and reply cellular morphology (Fig. 5 A).Research before shows that STAT3 is by suppressing transcription factor Twist to reduce expression and the accumulation EMT conversion of E-cadherin.We have detected protein expression and the rna transcription situation of Twist in PC-3M for this reason.Experimental result finds that lycorine process significantly can lower the mRNA (Fig. 5 B) of Twist, and increases pattern with the expression of E-cadherin and be consistent (Fig. 5 C).Simultaneously by the detection of on cell migration marker protein MMP2 and MMP9, find that lycorine can reduce the protein expression level of MMP2 and MMP9, confirm that lycorine can reverse the EMT of PC-3M really, and reduce its cell migration ability.
Embodiment six: the anti-prostate cancer activity of lycorine depends on the expression of STAT3
Technical method
1, immunoblotting (Western Blot) experimental technique and Migration experimental technique are as previously mentioned.
2, siRNA interference experiment
First according to the corresponding siRNA of document synthetic.After siRNA being proceeded to co-culture of cells 48h with Lipofectamin 2000, detect interference effect by the method for Western Blot.After continuing process 48h with variable concentrations medicine subsequently, detect the expression of corresponding protein with Western Blot.
Experimental result
DU145, LNCaP and PC-3M express not commensurability STAT3 and p-STAT3 (Fig. 5 E).Result display STAT3 and p-STAT3 of Fig. 5 F expresses maximum PC-3M and shows the most responsive to the effect of lycorine T suppression cell migration in Cell migration assay.Three strain cell lines also show significant difference (Fig. 5 F) statistically.After striking by siRNA the expression subtracting STAT3, the effect of lycorine to cell survival is also significantly reduced (Fig. 5 G).Above-mentioned experiment clearly shows that the anti-prostate cancer activity of lycorine depends on the expression of STAT3.
Embodiment seven: lycorine suppresses the STAT3 transcriptional activity of prostate gland cancer cell
Technical method
Immunoblotting (Western Blot) experiment and polymerase chain reaction (PolymeraseChainReaction, PCR) experiment are as previously mentioned.
Experimental result
Under the condition that EGF stimulates, lycorine suppresses the phosphorylation of STAT3 significantly, and this suppression, also along with the kinases of its upstream, comprises the dephosphorylation (Fig. 6 A) of JAK1 and JAK2.The CHIP experiment of Fig. 6 B shows that lycorine can reduce STAT3 to its typical downstream gene concentration dependant, as the DNA binding activity of Bcl-xL, cyclin D1 and Twist, and 10 μMs time, has especially significantly effect.These experiments prove growth and the transfer of lycorine by suppressing the transcriptional activity of STAT3 to inhibit carcinoma of prostate.
Claims (7)
1. Chinese herbal medicine monomer micromolecular compound lycorine or its hydrate or the pharmaceutically acceptable salt application in the medicine of preparation treatment prostate cancer disease, it is characterized in that, described lycorine has with following formula (I) structure:
2. apply as claimed in claim 1, it is characterized in that, described medicine comprises the medicine for the treatment of carcinoma of prostate malignant tumor.
3. apply as claimed in claim 1, it is characterized in that, described medicine be used alone or with other drug conbined usage.
4. apply as claimed in claim 1, it is characterized in that, described medicine is formulated into injectable fluid, aerosol, emulsifiable paste, gel, pill, capsule, syrup, transdermal patch or excipient.
5. a Chinese herbal medicine monomer micromolecular compound lycorine or its hydrate or pharmaceutically acceptable salt are in the application suppressing prostate cancer tumor cells propagation, growth, migration and infiltrate, it is characterized in that, described lycorine has with following formula (I) structure:
6. a pharmaceutical composition, is characterized in that, it contains such as formula the lycorine shown in (I) or its hydrate or pharmaceutically acceptable salt, and pharmaceutically acceptable carrier, and wherein, described lycorine has with following formula (I) structure:
7. pharmaceutical composition according to claim 6, is characterized in that, described pharmaceutical composition is formulated into injectable fluid, aerosol, emulsifiable paste, gel, pill, capsule, syrup, transdermal patch or excipient.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107198688A (en) * | 2016-03-18 | 2017-09-26 | 华东师范大学 | Application of the traditional Chinese medicine monomer lycorine in treatment breast cancer medicines are prepared |
| CN114042154A (en) * | 2021-12-14 | 2022-02-15 | 澳门大学 | Application of medicine composition in preparing anti-tumor combination therapy medicine |
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| CN1562022A (en) * | 2004-03-24 | 2005-01-12 | 中南大学 | Compound for treating leukemia and multiple myeloma |
| CN102178678A (en) * | 2011-03-18 | 2011-09-14 | 中国医学科学院医学实验动物研究所 | Application of lycorine in preparing medicament for treating diseases caused by human enterovirus 71 type infection |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1562022A (en) * | 2004-03-24 | 2005-01-12 | 中南大学 | Compound for treating leukemia and multiple myeloma |
| CN102178678A (en) * | 2011-03-18 | 2011-09-14 | 中国医学科学院医学实验动物研究所 | Application of lycorine in preparing medicament for treating diseases caused by human enterovirus 71 type infection |
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| MEICHUN HU ET AL: "Lycorine is a novel inhibitor of the growth and metastasis of hormone-refractory prostate cancer", 《ONCOTARGET》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107198688A (en) * | 2016-03-18 | 2017-09-26 | 华东师范大学 | Application of the traditional Chinese medicine monomer lycorine in treatment breast cancer medicines are prepared |
| CN114042154A (en) * | 2021-12-14 | 2022-02-15 | 澳门大学 | Application of medicine composition in preparing anti-tumor combination therapy medicine |
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Application publication date: 20150729 |