CN116350622A - Application of Pycnidone in preparation of anti-prostate cancer drugs - Google Patents
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- CN116350622A CN116350622A CN202310348556.9A CN202310348556A CN116350622A CN 116350622 A CN116350622 A CN 116350622A CN 202310348556 A CN202310348556 A CN 202310348556A CN 116350622 A CN116350622 A CN 116350622A
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- pycnidone
- prostate cancer
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Abstract
The invention discloses an application of Pycnidone in preparing an anti-prostate cancer drug, in particular an application of a necrotic apoptosis inducer Pycnidone in preparing the anti-prostate cancer drug, wherein the Pycnidone induces tumor cells to undergo necrotic apoptosis by activating DR3, so that the survival and proliferation of the tumor cells are inhibited, thereby inhibiting the development of tumors, and the Pycnidone is used for preparing the anti-prostate cancer drug.
Description
[ field of technology ]
The invention relates to the technical field of anti-prostate cancer drugs, relates to application of Pycnidone in preparing an anti-prostate cancer drug, and in particular relates to application of a necrotic apoptosis inducer Pycnidone in preparing the anti-prostate cancer drug.
[ background Art ]
Prostate cancer (PCa) refers to an epithelial malignancy that occurs in the Prostate. Prostate cancer is a global, male, high-grade disease. Data published by the cancer center in China shows that prostate cancer is ranked in the 6 th place of men in the 10 th place before the onset of major malignant tumors of nationwide sex, and 10.2 prostate cancer patients in every 10 thousands of people. The early stage of the prostate cancer is often asymptomatic, and as the tumor progresses, symptoms caused by the prostate cancer can be summarized as compression symptoms and metastasis symptoms. The compression symptoms are caused by the gradual increase of the prostate gland to compress the urethra, which causes the progressive urination difficulty, and are manifested by thin urine line, short range, slow urine flow, interruption of urine flow, dribbling after urination, incomplete urination and difficult urination, and furthermore, frequent urination, urgent urination, nocturia increase and even urinary incontinence. Tumor compression to the rectum may cause difficulty in stool or intestinal obstruction, compression to the vas deferens may cause ejaculatory deficit, compression to the nerves may cause perineal pain, and radiation to the sciatic nerve. In terms of metastatic symptoms, prostate cancer can invade the bladder, seminal vesicles, and vascular nerve bundles, causing hematuria, hemospermia, and impotence. Pelvic lymph node metastasis can cause edema of both lower limbs. Prostate cancer is often prone to bone metastases, causing bone pain or pathological fractures, paraplegia. Prostate cancer can also invade bone marrow causing anemia or a decrease in whole blood.
Androgen receptor (Androgen receptor, AR) plays an important role in the development of prostate cancer, and following the initiation of castration-induced androgen deprivation therapy by Huggins in 1941, scientists have increasingly clear knowledge of the intricate androgen signaling axis and AR, and androgen deprivation therapy (Androgen deprivation therapy, ADT) implemented in different forms of surgery, radiotherapy, drugs, etc., has become the standard treatment for high-risk localized prostate cancer, recurrent and advanced prostate cancer. Drug therapies targeting AR, gnRH, gnRHR, CYP A1 all fall into ADT therapy. After the patients receive these medications, the tumors in the body are temporarily suppressed. With the occurrence of events such as AR over-expression, cutter, gene mutation and the like, cancer cells in a patient resist ADT therapy, and at the moment, chemotherapy drugs such as docetaxel and the like are introduced for subsequent treatment, so that the survival time of the patient can be effectively prolonged. However, events such as altered tubulin interactions, altered efflux transporter expression, and overexpression of anti-apoptotic proteins, in turn, make cancer cells resistant to chemotherapy. Drug resistance, particularly endocrine therapy and chemotherapeutic drug cross-resistance, has become a major obstacle in current clinical practice.
Necroptosis is a self-destructive process of cells that prevents activation by the arrest of apoptosis. Necrotic apoptosis is usually triggered by extracellular stimuli, which when a ligand (e.g., TNF) binds to a death receptor (e.g., TNFR1, TLR 4) on the cell membrane, the receptor recruits TRADD, RIPK1/RIPK3, phosphorylating RIPK1/RIPK3 to form necrotic corpuscles; the necrotic bodies regulate MLKL phosphorylation, producing a membrane pore complex on the plasma membrane, leading to DAMP (damage associated molecular patterns) secretion, cell swelling and membrane rupture. Necrotic apoptosis is a different mechanism from that of apoptosis, and can occur after apoptosis is blocked, and may be a method of overcoming apoptosis resistance. It has also been found that necrotic apoptosis of tumor cells is also an immunogenic cell death, which stimulates the adaptive immune system, induces maturation of dendritic cells, cross-priming of cytotoxic T cells and production of IFN- γ, thereby activating an immune response against prostate cancer. Based on the conclusions reached by the above studies, targeting necrotic apoptosis has become an important strategy against prostate cancer.
[ invention ]
Aiming at the problem of drug resistance in the prior art, especially the problem of endocrine therapy and chemotherapy drug cross-resistance has become a major obstacle in the current clinical practice of resisting prostate cancer, the invention provides Pycnidone (namely conidiophore ketone, (1R, 3S,4R,14R,17E, 20R) -3,9,25-trihydroxy-4,11,16,16,20,27-hexamethyl-5, 21-dioxapentacyclic [ 18.9.0.0) 4,14 .0 6,12 .0 22,28 ]Icosahedron-6,9,11,17,22,25,27-heptaene-8, 24-dione) is used for preparing an anti-prostate cancer drug, and the inventor of the application discovers that Pycnidone can induce necrotic apoptosis of tumor cells by activating a DR3 signal pathway through extensive researches, so that the survival of the tumor cells and the development of tumors are inhibited.
The aim of the invention is achieved by the following technical scheme:
the application of the Pycnidone in preparing the anti-prostate cancer drugs, in particular to the application of the necrotic apoptosis inducer Pycnidone in preparing the anti-prostate cancer drugs, wherein the chemical structural formula of the Pycnidone is as follows:
furthermore, the application of the necrotic apoptosis inducer Pycnidone in preparing the anti-prostate cancer drugs means that the Pycnidone induces necrotic apoptosis of prostate tumor cells by activating a DR3 signal pathway, thereby inhibiting survival of the prostate tumor cells and inhibiting development of prostate tumor.
Further, the necrotic apoptosis inducer Pycnidone is selected from a monomer form of Pycnidone or a metabolic extract of marine microorganisms containing Pycnidone.
Preferably, the Pycnidione is provided in the form of a metabolic extract of the mangrove substrate sludge source fungus Penicillium sp.scsio 41411.
Furthermore, the application of the Pycnidone in preparing the anti-prostate cancer medicine is that the Pycnidone is used as a main component, a pharmaceutically acceptable carrier or excipient is added, or pharmaceutically acceptable auxiliary materials or auxiliary components are added to prepare a clinically acceptable medicine preparation, and the content of the Pycnidone is 1-99% (w/w), preferably 20-80% (w/w), more preferably 40-60% (w/w) based on the total weight of the medicine.
Further, the pharmaceutically acceptable carrier or excipient is selected from the group consisting of solvents, diluents, dispersants, suspending agents, surfactants, isotonic agents, thickening agents, emulsifiers, preservatives, binders, lubricants, stabilizers, hydration agents, emulsifying accelerators, buffers, absorbents, colorants, flavorants, sweeteners, ion exchangers, mold release agents, coating agents, flavoring agents, and antioxidants.
The medicament can be prepared into any one of powder, tablets, powder, capsules, pills, dripping pills, injection, emulsion, suspension or tincture, and the medicaments of the various dosage forms can be prepared according to a conventional method in the pharmaceutical field.
The terms "treating prostate cancer", "anti-prostate cancer" are used herein in their generic sense and refer herein in particular to the treatment of a mammalian subject, preferably a human, who has suffered from a prostate cancer disease according to the present invention with a medicament according to the present invention in order to treat, cure, alleviate, etc. the disease.
In this application, "pharmaceutically acceptable" means that there is no substantial toxic effect when used in the usual dosage amounts and thus can be approved by the government or by an international organization equivalent thereto or has been approved for use in animals, more particularly in humans, or registered in the pharmacopoeia.
The "pharmaceutically acceptable carrier or excipient" useful in the medicaments of the present invention may be any conventional carrier in the art of pharmaceutical formulation, and the choice of the particular carrier will depend on the mode of administration or type and state of disease used to treat the particular patient. Methods of preparing suitable drugs for particular modes of administration are well within the knowledge of those skilled in the pharmaceutical arts.
As used herein, the term "drug" has its ordinary meaning. In addition, the medicine of the invention can also exist or be provided in the forms of health care products, functional foods, food additives and the like. The pharmaceutical of the present invention can be prepared by extracting, separating and purifying the active ingredient of the raw material of the pharmaceutical of the present invention, optionally mixed with one or more pharmaceutically acceptable carriers or excipients, and then forming the desired dosage form, by using conventional techniques in the pharmaceutical field, particularly in the field of formulation, by extraction, separation and purification means commonly used in pharmaceutical production. The drug according to the present invention is a pharmaceutical preparation which can be suitably used for oral administration, parenteral administration or topical administration, and is particularly suitable for oral administration. Dosage forms for oral administration may include, for example, tablets, pills, hard or soft capsules, solutions, suspensions, emulsions, syrups, powders, granules, pellets, elixirs, and the like, without limitation thereto. These formulations may contain, in addition to the active ingredient, diluents (e.g. lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and glycine), lubricants (e.g. silica, talc, stearic acid or its magnesium, calcium and polyethylene glycols). The tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methyl cellulose, sodium carboxymethyl cellulose and polyvinylpyrrolidone. If necessary, it may further contain pharmaceutically acceptable additives such as disintegrants (e.g., starch, agar, alginic acid or sodium salt thereof), absorbents, colorants, flavoring agents, sweeteners, etc. The tablets may be prepared according to conventional mixing, granulating or coating methods.
Compared with the prior art, the invention has the following advantages:
1. at present, no clinically used anti-prostate cancer drug has the effect of targeting DR3 to play a role in resisting prostate cancer, and the application of the Pycnidone in preparing the anti-prostate cancer drug can be used as a substitute for the existing drug after drug resistance, and the Pycnidone can activate DR3 to induce cells to undergo necrotic apoptosis and inhibit survival of prostate cancer cells, so that the development of prostate cancer is inhibited, and the Pycnidone is used for preparing the anti-prostate cancer drug.
2. At present, the first-line chemotherapeutic medicine for clinically treating the prostate cancer is a tublin inhibitor, and tublin is cytoskeletal protein and is expressed in normal cells abundantly, so that the side effect generated by the treatment of the tublin inhibitor is larger. The Pycnidone plays a role in mediating necrotic apoptosis by targeting DR3, DR3 is a death receptor, and the expression in tumor cells is higher than that of normal cells, so that the Pycnidone has better selectivity and smaller toxicity to normal cells. The invention relates to an IC for inhibiting the viability of prostate cancer cells by using Pycnidone 50 Low; has small cytotoxicity to normal prostate and high Selection Index (SI), which shows that the Pycnidone has good selectivity to prostate cancer cells and has side effect smaller than that of a tublin inhibitor.
3. At present, no clinically used anti-prostate cancer drug is a necrotic apoptosis inducer, most of the drugs are apoptosis inducers, necrotic apoptosis is a mode of continuously inducing cell death after cell apoptosis is blocked, and the application of the Pycnidone in preparing the anti-prostate cancer drug can be used as a supplementary selection of the existing apoptosis-inducing drug or a combination therapy drug selection.
4. The application of the Pycnidone in preparing the anti-prostate cancer drugs discovers that the Pycnidone firstly induces necrotic apoptosis by targeting DR3 and then inhibits the expression of Androgen Receptor (AR) to further limit the survival of prostate cancer cells; the activity of the Pycnidone for inhibiting the prostate cancer cells in vitro is obviously superior to that of a second-generation androgen receptor antagonist enzalutamide; the 1 mu M Pycnidone has the equivalent effect of inhibiting the expression of androgen receptor target genes KLK3 and TMPRSS2 of prostate cancer cells to 10 mu M enzalutamide. The Pycnidone provided by the invention can be used as a supplementary choice or a combination therapy drug selection after drug resistance of androgen receptor antagonists such as enzalutamide.
[ description of the drawings ]
In order to more clearly illustrate the embodiments of the invention or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, it being obvious that the drawings in the following description are only some embodiments of the invention, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a graph showing the effect of Pycnidone on PC-3, 22Rv1, DU145, LNCaP, VCaP, WPMY-1, LNCaP cell survival in the examples of the present invention (wherein A is the result of Pycnidone inhibiting PC-3, 22Rv1, DU145, LNCaP, VCaP, WPMY-1 cell survival; B is the result of Pycnidone inhibiting LNCaP cell survival);
FIG. 2 is a graph showing that in the embodiment of the invention, the Pycnidone induces the LNCaP cells to undergo necrotic apoptosis (wherein A is the result of the observation under a transmission electron microscope that after the LNCaP cells are treated by the Pycnidone, the cytoplasmic membrane is broken, the cytoplasm is semitransparent, the organelle swells and the nuclear membrane remains, which indicates that the cells undergo necrotic apoptosis; and B is the result of the upregulation of MLKL protein phosphorylation by the Pycnidone);
FIG. 3 is a diagram showing the binding of Pycnidone to DR3 protein in examples of the present invention;
FIG. 4 is a graph showing the effect of Pycnidone on AR and mRNA and protein expression of its target genes in the examples of the present invention (wherein A is the effect of Pycnidone on AR gene expression, B is the effect of Pycnidone on KLK3 gene expression, C is the effect of Pycnidone on TMPRSS2 gene expression, D is the effect of Pycnidone on AR, KLK3, TMPRSS2 protein expression, E is the effect of Pycnidone on AR nuclear translocation);
FIG. 5 is a graph of the inhibition of prostate cancer progression in zebra fish by Pycnidone in an example of the present invention (wherein A is the tumor size of each group prior to administration of the zebra fish prostate cancer model; and B is the tumor size of each group of the zebra fish prostate cancer model after 72 hours of administration treatment).
[ detailed description ] of the invention
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The following describes the invention in more detail with reference to examples.
Examples:
application of Pycnidone in preparing anti-prostate cancer drugs:
the Pycnidone is provided in the form of a metabolic extract of the mangrove substrate sludge source fungus Penicillium sp.SCSIO 41411.
The fungus Penicillium sp.SCSIO41411 was deposited at the Cantonese microbiological culture Collection center (GDMCC) at month 8 and 4 of 2022, address: building 5, guangzhou city, first, china, no. 100, university, no. 59, university of Guangdong university, institute of microorganisms, post code: 510070 it is deposited under the accession number GDMCC No:62687
Taking PC-3, 22Rv1, DU145, LNCaP, VCaP prostate cancer cells and WPMY-1 normal prostate cells in logarithmic growth phase, inoculating the cells into a 96-well cell culture plate with a complete culture solution containing 10% FBS, and inoculating 5000 cells per well; after the cells are all attached, adding Pycnidone with different concentrations; culture in LNCaP cellIn the culture plate, the concentration of Pycnidone reaches 10 -12 mol/L、10 -11 mol/L、10 -10 mol/L、10 -9 mol/L、10 -8 mol/L、10 -7 mol/L、10 -6 mol/L、10 -5 mol/L; in the culture plate inoculated with PC-3, 22Rv1, DU145, VCaP, WPMY-1 cells, the concentration of Pycnidone was brought to 0.3125. Mu. Mol/L, 0.625. Mu. Mol/L, 1.25. Mu. Mol/L, 2.5. Mu. Mol/L, 5. Mu. Mol/L, 10. Mu. Mol/L, 20. Mu. Mol/L, 40. Mu. Mol/L; DMSO was added to the control group to achieve a concentration of 0.1%; after 72 hours of compound treatment of cells, 10. Mu.L/well MTT solution (5 mg/mL) was added to the culture, the cells were reacted with MTT in an incubator for 4 hours, then the cell culture plates were removed, OD values at 570nm were detected, and IC was fitted with GraphPad Prism 8.0 50 A value;
as shown in fig. 1, pycnidione can inhibit the cell viability of prostate cancer cells and normal prostate cells to varying degrees; IC for inhibiting WPMY-1 activity of normal prostate cells 50 IC for inhibiting prostate cancer cells PC-3, 22Rv1, DU145, VCaP, LNCaP at 1.092. Mu.M 50 3.141. Mu.M, 1.137. Mu.M, 20.62. Mu.M, 9.026. Mu.M, 79.76nM, respectively (FIGS. 1A, 1B); pycnidione was most selective for LNCaP prostate cancer cells relative to normal prostate cells, with a selectivity index of 13.69 (fig. 1B); the data demonstrate that Pycnidione has the effect of inhibiting prostate cancer cell viability, wherein the inhibition effect on LNCaP cells is most remarkable;
FIG. 1 effect of Pycnidone on prostate cancer cell viability;
experimental 2, transmission electron microscope and Western blot technique detect that Pycnidone induces prostate cancer cells to generate necrotic apoptosis
LNCaP cells are inoculated into a 6-well plate, pycnidone is added after the cells are completely adhered to the plate, the concentration is 1 mu M, and a blank control group is added with a complete culture solution containing 0.1% DMSO; collecting cells 24 hours after the compound is acted, fixing the cells by using an electron microscope fixing solution, and then preparing ultrathin cell slices; the morphology of LNCaP cells treated for 24 hours was observed using transmission electron microscopy Pycnidione (Pyc), and it was found that Pyc treated plasma membrane rupture, cytoplasmic translucency, organelle swelling, nuclear membrane retention, in comparison to untreated cells (FIG. 2A), suggested that necrotic apoptosis occurred in the cells (FIG. 2B); in addition, phosphorylation of MLKL protein at Ser358 site is a key step in initiating necrotic apoptosis, while p-MLKL (Ser 358) expression was significantly increased after Pyc treatment of LNCaP cells (fig. 2C), which found that Pyc was molecularly verified to induce necrotic apoptosis;
FIG. 2 Pycnidone induces necrotic apoptosis of LNCaP cells and upregulates MLKL protein phosphorylation;
experiment 3, pycnidone has a high binding affinity to DR3
The binding Affinity of the Pycnidone and the protein related to necrotic apoptosis is calculated by adopting a molecular docking technology (Autodock Vina), and the Pycnidone is found to be embedded into an active pocket of the DR3 protein by forming more hydrophobic force and hydrogen bond force to interact with the DR3 protein, the Affinity is-13.0 kcal/mol, the detected Ki is 0.3nM,Ligand Efficiency is-0.3, and the Pycnidone is suggested to have the best Affinity with the DR3 protein (table 1, figure 3);
TABLE 1 binding affinity of Pycnidone to necrotic apoptosis-related proteins
FIG. 3 molecular interaction information of Pycnidone and DR3
LNCaP cells were seeded in 6-well plates and 60mm dishes, and after the cells were completely adherent, pycnidone was added (3 Pycnidone treatment groups were set at 0.01. Mu.M, 0.1. Mu.M, 1. Mu.M, and experiments were repeated 3 times), the blank control group was added with complete medium containing 0.1% DMSO, agonist control group 10nM DHT, inhibitor control group 10. Mu.M enzalutamide; collecting cells 24 hours after the compound is acted on, and extracting total RNA and total protein; mRNA and protein expression of AR, KLK3 (PSA), TMPRSS2 were then detected by qPCR and Western Blot, respectively; qPCR results showed that Pycnidone inhibited AR mRNA expression in a dose-dependent manner in the 0.01-1. Mu.M concentration interval, inhibited mRNA expression of AR target gene (KLK 3, TMPRSS 2), and that 1. Mu.M Pycnidone inhibited effect equivalent to 10. Mu.M enzalutamide (FIGS. 4B, 8C); the Western blot results showed that Pycnidione also inhibited protein expression of AR and its target gene (fig. 4D); in addition, the results of cellular immunofluorescence staining showed that Pycnidione had a stronger effect of inhibiting AR nuclear translocation than enzalutamide (fig. 4E);
FIG. 4 Pycnidone down-regulates AR and target gene expression;
experiment 5 Pycnidone inhibits prostate cancer progression in zebra fish
Zebra fish breeding: adult zebra fish are cultured in a zebra fish circulating water culture system, the water temperature is kept at (28.5+/-1) DEG C, and the pH value is NaHCO 3 Adjusting, keeping the electrical conductivity at about 7.0 and 450-500 mu s/cm, and regulating and controlling the life cycle of the zebra fish by using an artificial light source, wherein the illumination cycle is that the brightness and the darkness are 14:10 alternately; the bait is selected from hatched live brine shrimp, and is fed for 2 times a day; the fish is matched according to the proportion of female to male of 1:1 or 2:1 at night in the day before spawning; after the next day of spawning is completed, collecting eggs, placing the eggs in a plate, removing dead eggs, excrement and other sundries, cleaning the eggs with fish-farming water for 3 times, and transferring the eggs into a constant temperature incubator at 28.5 ℃ for culturing;
cell staining: log-growing LNCaP cells were taken, centrifuged after digestion, the supernatant was aspirated, the cells were resuspended in 3mL PBS, counted and removed 2 x 10 7 Cell suspension is carried out by using PBS to obtain a volume of 1mL, then 5 mu L of CM-DiI Cell-Labeling Solution is added, a liquid-transferer is used for gently blowing the Cell suspension, and then the Cell is placed into a culture box at 37 ℃ for incubation for 20min; then centrifuging at room temperature at 1500rpm for 5 minutes, washing the cells with the culture solution at 37 ℃ for 3 times, and finally re-suspending the cells with 50 mu L of the culture solution for later use, and placing the cells on ice;
establishing a zebra fish allograft prostate cancer cell tumor model: 120 zebra fish with normal development and 48hpf embryo period are selected, and are anesthetized by 0.1 percent fish ballast for standby; filling the prepared 22Rv1 cells into a microinjection needle, dripping a drop of liquid paraffin on a bench micro scale, and placing the bench micro scale under a microscope; injecting cells into liquid paraffin to adjust the cells to a target volume; placing anesthetized zebra fish on an agarose model prepared in advance, and beginning to inject cells into yolk sac of the zebra fish under a microscope, wherein each fish is injected with 1-2nL of cell suspension, and the cell suspension approximately contains 400-800 cells;
administration: judging the zebra fish successfully screened and modeled according to the fluorescence display condition of the yolk sac under a microscope; randomly dividing the zebra fish successfully molded into 2 groups of 20 zebra fish; vehicle group (not administered), 1 μm Pycnidione group, respectively; performing pharmaceutical intervention according to the group;
after administration, observing the general condition of zebra fish every day, and removing dead fish; observing under a microscope after 3 days of administration, photographing and recording the fluorescence condition in the zebra fish; analyzing the pictures by utilizing image J software, quantitatively analyzing the fluorescence areas of each group, and evaluating the growth inhibition effect of the drug intervention of different groups on tumors in the zebra fish body; the results showed that LNCaP cells clustered in zebra fish yolk sac before the grouping treatment (fig. 5A); after grouping treatment, prostate cancer cells in the Vehicle group zebra fish spread to the near and far ends of the yolk sac; the fluorescence area of the cell mass of the prostatic cancer in the Pycnidone group is reduced, and the cell mass of the prostatic cancer does not spread to other parts in the zebra fish body, which indicates that the Pycnidone effectively inhibits the development of prostatic cancer in the zebra fish body.
The results show that:
pycnidone induces necrotic apoptosis of prostate tumor cells by activating DR3 signaling pathway, thereby inhibiting survival of prostate tumor cells and inhibiting prostate tumor development.
Pycnidione has a remarkable effect of inhibiting prostate cancer at both cellular and animal levels.
At the same concentration, the effect of Pycnidone in inhibiting the prostate cancer is better than that of the second-generation androgen receptor antagonist enzalutamide.
The action target point of the Pycnidone is DR3, is completely different from the action target point of the existing medicine for treating the prostatic cancer, and can be used as a supplementary selection or combined treatment medicine after the existing medicine is resistant.
In conclusion, the application of the necrotic apoptosis inducer Pycnidone in preparing the anti-prostate cancer drugs suggests that the Pycnidone has potential therapeutic effects on prostate cancer and has good clinical application prospect.
The application of the Pycnidone provided by the invention in preparing medicaments for treating prostate cancer is described in detail above. The principles and embodiments of the present invention have been described in this application with reference to specific examples, which are intended to be merely illustrative of the methods of the present invention and their central ideas. It should be noted that it will be apparent to those skilled in the art that various changes and modifications can be made herein without departing from the principles of the invention, which also falls within the scope of the appended claims.
Claims (7)
- The application of Pycnidone in preparing anti-prostate cancer drugs is characterized in that: is application of Pycnidone serving as necrotic apoptosis inducer in preparing anti-prostate cancer medicine, wherein the Pycnidone is conidiophore ketone, namely (1R, 3S,4R,14R,17E, 20R) -3,9,25-trihydroxy-4,11,16,16,20,27-hexamethyl-5, 21-dioxapentacyclic [18.9.0.0 ] 4,14 .0 6,12 .0 22,28 ]Icosahedron-6,9,11,17,22,25,27-heptaene-8, 24-dione has a chemical structural formula as follows:
- 2. the use of Pycnidione according to claim 1 for the preparation of an anti-prostate cancer medicament, characterized in that: refers to that the Pycnidone induces necrotic apoptosis of prostate tumor cells by activating a DR3 signal pathway, thereby inhibiting survival of the prostate tumor cells and inhibiting development of the prostate tumor.
- 3. The use of Pycnidione according to claim 1 for the preparation of an anti-prostate cancer medicament, characterized in that: the necrotic apoptosis inducer Pycnidone is selected from a monomer form of Pycnidone or a marine microorganism metabolic extract containing Pycnidone.
- 4. Use of Pycnidione according to claim 3 for the preparation of an anti-prostate cancer medicament, characterized in that: the Pycnidone is provided in the form of a metabolic extract of the mangrove substrate sludge source fungus Penicillium sp.SCSIO 41411.
- 5. The use of Pycnidione according to claim 1 for the preparation of an anti-prostate cancer medicament, characterized in that: the medicine is a clinically acceptable medicine preparation prepared by taking the Pycnidone as a main component and adding pharmaceutically acceptable carriers or excipients or adding pharmaceutically acceptable auxiliary materials or auxiliary components, and the content of the Pycnidone is 1-99% w/w based on the total weight of the medicine.
- 6. The use of Pycnidione according to claim 5 for the preparation of an anti-prostate cancer medicament, characterized in that: the content of the Pycnidone is 20-80% w/w.
- 7. The use of Pycnidione according to claim 6 for the preparation of an anti-prostate cancer medicament, characterized in that: the content of the Pycnidone is 40-60% w/w.
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