CN116350621A - Application of 12-O-deacetyl-photomoxanthone A in preparation of ovarian cancer resisting medicine - Google Patents
Application of 12-O-deacetyl-photomoxanthone A in preparation of ovarian cancer resisting medicine Download PDFInfo
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Abstract
The invention discloses a compound 12-OApplication of deacetyl-phomoxantrone A in preparation of anti-ovarian cancer drugs, and the invention discovers that the compound 12-ODeacetyl-phomoxanine a significantly inhibits the viability of ovarian cancer SKOV3, a2780 cells in a time-dose dependent manner, with an inhibition comparable to, or even stronger than that of the positive drug cisplatin; 12-OThe formation of SKOV3 cell clone can be reduced after the deacetyl-phomoxanne A treatment, the transverse migration, longitudinal migration and invasion capacity of SKOV3 cells can be obviously inhibited, and the apoptosis of ovarian cancer SKOV3 cells can be induced; the research results show that: compound 12-OThe deacetyl-phomoxantrone A has obvious anti-ovarian cancer activity and can be used for preparing anti-ovarian cancer medicines. The invention discloses a compound 12-O‑deacethe novel application of tyl-phomoxantrone A provides a novel medicine source for the treatment of ovarian cancer and a novel approach for the treatment and cure of ovarian cancer.
Description
Technical Field
The invention belongs to the technical field of medical biology, relates to a new application of a compound, and in particular relates to an application of a compound 12-O-deacetyl-phomoxantone A in preparation of an anti-ovarian cancer drug.
Background
Ovarian cancer (ovarian cancer) is one of the common malignant tumors of the female reproductive system, the incidence of which is the second most posterior to endometrial cancer, but the mortality of which is the first of gynecological tumors. Ovarian cancer can occur at any age, but most occur during the period of ovarian function from vigorous to weak, generally seen in menopausal and menopausal women. In recent years, the incidence and mortality rate of ovarian cancer have increased, severely threatening the health of women. At present, an integrated treatment method of surgical excision and auxiliary chemotherapy is adopted for clinically treating ovarian cancer, paclitaxel and platinum drugs (cisplatin or carboplatin) combined chemotherapy is a specimen chemotherapy scheme for treating ovarian cancer, and topotecan, doxorubicin, etoposide, gemcitabine and the like are used as second-line treatment drugs for treating ovarian cancer patients. The application of chemotherapy drugs such as taxol, platinum drugs and the like can obviously improve the survival rate of ovarian cancer patients. However, the therapeutic effect of chemotherapeutic agents is still unsatisfactory due to limitations in the problems of non-response, tolerability and toxic side effects of chemotherapy, etc. Therefore, while improving the surgical treatment, development of a safe and effective novel medicament for treating ovarian cancer is urgent to improve the treatment effect of ovarian cancer.
The compound 12-O-deacetyl-photomoxanthone A related by the invention has the Chinese name: 12-O-deacetyl-phosphaxanthone A, the molecular formula is: c (C) 36 H 36 O 15 12-O-deacetyl-phomoxantone A was isolated for the first time from the rice fermentation product of the endophytic fungus Phomopsis glonicolola of the mangrove plant Mulberry (Pro-Apoptotic and ImmunostimulatoryTetrahydroxanthone Dimers from the Endophytic Fungus Phomopsislongicolla [ J)].The Journal of Organic Chemistry，2013，78 (24): 12409-12425), the results of the activity screening experiments show that the cell line has a strong proliferation inhibition effect on lymphoma cell line L5178Y. Then found in rice fermentation products of endophytic fungus Phomopsis sp. Of the mangrove plant Rhizophora mucronata (Isolation of a phomoxanthone A derivative, a new metabolite of tetrahydroxanthone, from a Phomopsis sp. Isolated from the mangrove, rhizho mucronata. [ J)]Natural product communications,2013,8 (12): 1735-1737). The compound 12-O-deacetyl-photomoxanthone a belongs to a xanthone derivative, and most of the xanthone derivatives often exhibit a wide range of biological and pharmacological activities due to the phenolic functional groups on the three rings of which they are linearly arranged; up to now, xanthone derivatives have been reported to have antifungal, antioxidant, liver protecting, antiviral, antimalarial effects, etc. At present, no related research report is yet seen on the aspect of resisting ovarian cancer of a compound 12-O-deacetyl-phomoxantone A.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a new application of the compound 12-O-deacetyl-photomoxanthone A, in particular to an application of the compound 12-O-deacetyl-photomoxanthone A in preparing an anti-ovarian cancer drug, and provides a new drug source for treating ovarian cancer.
In order to achieve the above purpose, the invention adopts the following technical scheme: application of 12-O-deacetyl-photomoxanthone A in preparing anti-ovarian cancer drugs, wherein the Chinese name of the compound 12-O-deacetyl-photomoxanthone A is as follows: 12-O-deacetyl-phosphaxanthone A, the molecular formula is: c (C) 36 H 36 O 15 The chemical structural formula is as follows:
the application of the 12-O-deacetyl-phomoxantone A in preparing the anti-ovarian cancer medicine is characterized in that the compound 12-O-deacetyl-phomoxantone A is singly or additionally provided with one or more pharmaceutically acceptable carriers or auxiliary materials to prepare a clinically acceptable pharmaceutical preparation for treating ovarian cancer.
The application of the 12-O-deacetyl-photomoxanthone A in preparing an anti-ovarian cancer drug is that the anti-ovarian cancer drug inhibits proliferation of ovarian cancer cells and/or promotes apoptosis of ovarian cancer cells.
The inventor researches the influence of a compound 12-O-deacetyl-phomoxantone A (12-ODPXA) on ovarian cancer through experimental methods such as CCK8, cell clone formation experiments, scratch experiments, transwell migration and invasion, AO-EB fluorescent double-dyeing and the like, and the experimental results show that: the 12-ODPXA remarkably inhibits the activity of ovarian cancer SKOV3 and A2780 cells in a time-dose dependent manner, and the inhibition effect is equivalent to or even stronger than that of a positive drug cisplatin; the IC50 values of the 12-ODPXA on the SKOV3 and A2780 cells at 48h and 72h are less than 10 mu M; the formation of SKOV3 cell clone can be reduced after 12-ODPXA treatment, and the lateral migration, longitudinal migration and invasion capacity of SKOV3 cells can be obviously inhibited; 12-ODPXA can induce apoptosis of ovarian cancer SKOV3 cells.
The Western blot experiment result shows that: the 12-ODPXA stem prognosis can influence the migration and invasion of SKOV3 cells and the expression level of EMT-related proteins, such as down-regulating protein expression of MMP-2, MMP-9, vimentin and N-Cadherin; the 12-ODPXA treatment can also regulate the expression level of protein related to apoptosis of SKOV3 cells, wherein the expression of the pro-apoptotic protein Bax can be up-regulated, and the expression of the apoptotic protein Bcl-2 can be down-regulated.
The beneficial effects of the invention are as follows:
according to the invention, the compound 12-O-deacetyl-photomoxanthone A can obviously inhibit the activity of ovarian cancer cells, can effectively inhibit proliferation, migration and invasion of the ovarian cancer cells, and induces apoptosis of the ovarian cancer cells, and the research result shows that: the compound 12-O-deacetyl-photomoxanthone A has obvious anti-ovarian cancer activity and can be used for preparing anti-ovarian cancer medicines. The invention discloses a new application of the compound 12-O-deacetyl-phomoxantrone A in preparing an anti-ovarian cancer drug for the first time, provides a new drug source for treating ovarian cancer, provides a new way for treating and curing ovarian cancer, has good development and application prospects, and provides a basis for the application of the compound 12-O-deacetyl-phomoxantrone A in treating ovarian cancer.
Drawings
FIG. 1 shows the proliferation inhibition effect of CCK8 method on different ovarian cancer cell lines after detecting the effects of 12-ODPXA and DDP with different concentrations for 24, 48 and 72 hours;
FIG. 2 effect on SKOV3 cell clonogenic potential following ODPXA action;
FIG. 3 is a graph showing the results of an experiment for inhibiting migration and invasion of ovarian cancer cells by ODPXA, wherein A: scratch experiments detect the influence of different concentrations of 12-ODPXA on the lateral migration of ovarian cancer SKOV3 cells for 24 hours; b: a scratch test cell mobility statistic graph, comparing P <0.05, P <0.01, P <0.001, P <0.0001 with a Control group (Control);
FIG. 4 is a graph showing the results of an ODPXA test for inhibiting migration and invasion of ovarian cancer cells, wherein A: transwell migration experiments detect the influence of different concentrations of 12-ODPXA action for 24 hours on the longitudinal migration of ovarian cancer SKOV3 cells; b: transwell experiment migration cell count profile, compared to Control (Control) P <0.05, P <0.01, P <0.001, P <0.0001;
FIG. 5 is a graph showing the results of an experiment for inhibiting migration and invasion of ovarian cancer cells by ODPXA-Transwell invasion, wherein A: transwell invasion experiments detect the influence of different concentrations of 12-ODPXA action for 24 hours on the invasion capacity of ovarian cancer SKOV3 cells; b: transwell experimental invasion cell count profile, compared to Control (Control) P <0.05, P <0.01, P <0.001, P <0.0001;
FIG. 6 is a graph showing the results of a double fluorescent dye experiment of apoptosis-AO-EB induced by ODPXA in ovarian cancer cells, wherein A: observing apoptosis morphology of SKOV3 cells after 12-ODPXA treatment for 24 hours by using an AO-EB double staining method;
FIG. 7-ODPXA inducing apoptosis of ovarian cancer cells, wherein A: detecting the proportion of apoptotic cells in SKOV3 cells after the 12-ODPXA with different concentrations acts for 24 hours in a flow mode; b: a stream data statistical graph;
FIG. 8 effects of ODPXA on levels of expression of ovarian cancer SKOV3 cells MMP-2, MMP-9, vimentin, N-Cadherin, bax, bcl-2 proteins.
Detailed Description
The present invention will be further described with reference to the following examples, in which all of the experimental methods used are conventional methods and materials, reagents, etc. are commercially available from chemical reagent company unless otherwise specified.
Example 1
Anti-ovarian cancer action and mechanism study of 12-O-deacetyl-photomoxanthone A (12-ODPXA)
1.12 influence of ODPXA on proliferation potency of ovarian cancer cells
1.1CCK8 experiment
1.1.1 Experimental methods
Taking ovarian cancer SKOV3 and A2780 cells in logarithmic growth phase, digesting with pancreatin, collecting cells, adding 1640 complete culture medium, and blowing and mixing to prepare cell suspension. After counting, the inoculation density of the A2780 cells is adjusted to be 5 multiplied by 10 4 cell/mL, SKOV3 cell seeding Density of 3×10 4 cell/mL, inoculating to 96-well plate, each 100 μl, arranging blank control group, positive control group, and administration group, each group having 3 multiple wells, placing at 37deg.C and 5% CO 2 Is cultured in a constant temperature incubator. After 24h incubation, old solution was aspirated, the blank control was added to complete medium, the positive control was added to 100. Mu.L of complete medium containing cisplatin (DDP) at various concentrations, and the dosing group was added to 100. Mu.L of complete medium containing 12-ODPXA at various concentrations. After culturing for 24, 48, 72 hours, the old solution was aspirated, 10. Mu.L of CCK8 working solution and 90. Mu.L of medium were added to each well, and incubated in a cell incubator for 1 hour. Absorbance values (OD) were measured at 450nm using a microplate reader. The measurement was repeated 3 times, and the cell viability of the control group was taken as 100%, and the calculation formula of the cell viability of each group was as follows:
cell viability = [ (As-Ab)/(Ac-Ab) ] ×100%
Inhibition ratio = [ (Ac-As)/(Ac-Ab) ]. Times.100%
As, absorbance of experimental wells (containing cells, medium, CCK-8 solution and drug solution);
ac: control well absorbance (cell, medium, CCK-8 solution, drug free);
ab-blank well absorbance (Medium, CCK-8 containing solution, no cells, drug).
1.1.2 experimental results
The experimental results are shown in tables 1-4 and attached figure 1, and the results show that 12-ODPXA can obviously inhibit the activity of ovarian cancer SKOV3 and A2780 cells in a time-dose dependent manner, and the inhibition effect is equivalent to or even stronger than that of the positive drug cisplatin. The IC50 values of 12-ODPXA on SKOV3 and A2780 cells at 48h and 72h were less than 10. Mu.M.
TABLE 1 influence of 12-ODPXA, cisplatin on the viability of ovarian cancer SKOV3 cells
TABLE 2 influence of 12-ODPXA and cisplatin on ovarian cancer A2780 cell viability
TABLE 3 12 ODPXA and cisplatin action on ovarian cancer SKOV3 cell IC 50 Value of
TABLE 4 12 ODPXA and cisplatin action on ovarian cancer A.2780 cell IC 50 Value of
1.2 cell clone formation experiments
1.2.1 Experimental methods
SKOV3 cells in the log phase were plated uniformly at a density of 400 cells/well in 6-well plates. After overnight incubation, diluted 12-ODPXA was added to give final drug concentrations of 0. Mu. Mol/L (control), 2. Mu. Mol/L, 4. Mu. Mol/L, 8. Mu. Mol/L, 3 wells per group, respectively. The old medium was discarded 48h after dosing, cells were cultured with complete medium and observed for colony formation. After 10-14 days of culture, the supernatant was discarded, the cells were washed with PBS for 2 times, fixed with 100% methanol for 30min, and then stained with 1% crystal violet stain for 20min. Excess dye liquor was washed with distilled water and then photographed.
1.2.2 experimental results
The formation of SKOV3 cell clones was reduced after 12-ODPXA treatment, and the number of cell clones formed decreased with increasing doses administered, as shown in FIG. 2.
2.12 influence of ODPXA on the cell migration and invasion ability of ovarian cancer cells
2.1 scratch test
2.1.1 Experimental methods
A2780 cell and SKOV3 cell with good growth state are uniformly spread on a 6-well plate. When the cells were completely fused, the wells were scored vertically to the bottom horizontal line with a 200. Mu.L gun tip. The scraped cells in the well plate were washed out with PBS and replaced with drugs diluted with low concentration serum medium at concentrations of 0. Mu. Mol/L (control), 2. Mu. Mol/L, 4. Mu. Mol/L, 8mol/L, 3 multiplex wells per group, respectively. At the time of dosing for 0h and 24h, the scratch condition at the same position is observed and photographed under a microscope. The migration was observed and the scratch area was detected using Image-j software. Calculate cell mobility, mobility= (T 0h area-T 24h area)/T 0h Area×100%.
2.1.2 experimental results
The experimental results are shown in Table 5 and figure 3, and the scratch experiment shows that the 12-ODPXA treatment can obviously inhibit the lateral migration of SKOV3 cells, the scratch area of the administration group is larger than that of the control group at 24 hours, and the cell mobility is reduced after the administration.
TABLE 5 influence of 12-ODPXA on SKOV3 cell scratch test mobility
2.2Transwell migration experiments
2.2.1 Experimental methods
Cells were digested, centrifuged after termination of digestion to discard the culture, washed 1-2 times with PBS, and resuspended in serum-free medium. Cell density was adjusted to 2X 10 5 /ml. 100 μl of the cell suspension was added to the Transwell chamber. 600 μl of complete medium was added to the 24-well plate lower chamber. At 37 ℃,5% CO 2 The incubator cultures for 24 hours. The culture medium in the upper chamber is sucked and changed into serum-free culture medium containing 12-ODPXA with different concentrations, so as to ensure that the final cultureThe concentration is 0 mu mol/L (control group), 2 mu mol/L, 4 mu mol/L and 8 mu mol/L respectively, and the culture is continued in an incubator for 24 hours respectively; taking out the Transwell chamber, carefully washing off residual culture medium with PBS, and fixing cells which pass through the chamber, enter the lower chamber and grow on the wall for 30min with 100% methanol; removing the fixing solution, then dyeing with 0.1% crystal violet solution for 30min, carefully washing off crystal violet with distilled water, and wiping off residual cells on the inner side of the Transwell cell with a cotton swab; after Transwell natural air drying, 4 visual fields are randomly selected under a microscope to be photographed, image J software is used for counting, and three repeated experiment results are counted on a graph pad Prism 9.
2.2.2 experimental results
The results of the experiment are shown in Table 6 and FIG. 4, and the transwell migration experiment shows that the number of migrated cells can be reduced after the 12-ODPXA is acted, which shows that the migration can inhibit the longitudinal migration of SKOV3 cells.
TABLE 6 influence of 12-ODPXA on the number of migrating cells in SKOV3 cell Transwell experiments
2.3Transwell invasion experiments
2.3.1 Experimental methods
Matrigel was taken out of the-20 ℃ refrigerator one day in advance and left to melt overnight at 4 ℃. Diluting the matrix collagen liquid with serum-free culture medium at a ratio of 1:8 in an ultra clean bench with a gun head precooled at 4deg.C, and performing above steps on ice to prevent matrix gelatin from solidifying. 50 μl of diluted Matrigel gel was spread on the upper chamber of the Transwell chamber, ensuring that Matrigel was uniformly spread over the bottom (note that neither the bottom of the chamber nor the interior of Matrigel had bubbles), and the Matrigel was incubated in an incubator at 37deg.C for 2-3h to promote Matrigel clotting. Cells were digested, centrifuged after termination of digestion, and the culture was discarded (washed 1-2 times with PBS) and resuspended in serum-free medium. Adjusting cell density to 2×10 5 /ml. 100 μl of the cell suspension was added to the Transwell chamber. 600 μl of complete medium was added to the 24-well plate lower chamber at 37deg.C with 5% CO 2 The incubator cultures for 24 hours. The culture medium in the upper chamber was aspirated and replaced with serum-free medium containing 12-ODPXA at different concentrations to a final concentration of 0. Mu. Mol +.L (control group), 2 mu mol/L, 4 mu mol/L and 8 mu mol/L, and continuously placing the culture medium into an incubator to be respectively cultured for 24 hours; taking out the Transwell chamber, carefully washing off residual culture medium with PBS, and fixing cells which pass through the chamber, enter the lower chamber and grow by adherence for 30min with methanol; removing the fixing solution, then dyeing with 0.1% crystal violet solution for 30min, carefully washing off crystal violet with distilled water, and wiping out matrigel and residual cells on the inner side of the Transwell cell with a cotton swab; after Transwell natural air drying, 4 visual fields are randomly selected under a microscope to be photographed, image J software is used for counting, and three repeated experiment results are counted on a graph pad Prism 9.
2.3.2 experimental results
The results of the experiment are shown in Table 7 and FIG. 5, and the transwell invasion experiment shows that the 12-ODPXA can reduce the number of invading cells after the effect, thus demonstrating the capability of inhibiting the invading ability of SKOV3 cells.
TABLE 7 influence of 12-ODPXA on the number of invading cells of SKOV3 cell Transwell experiments
3.12-ODPXA study on apoptosis induction of ovarian cancer cells
3.1 AO-EB fluorescent double-dyeing
3.1.1 Experimental methods
SKOV3 cells with good growth status were cultured at 1.5X10 5 The cells/wells were spread evenly in 6-well plates at 37℃with 5% CO 2 Is cultured in a constant temperature cell incubator. After 24h incubation, 12-ODPXA diluted in complete medium was added to give final concentrations of 0. Mu. Mol/L (control), 2. Mu. Mol/L, 4. Mu. Mol/L, 8. Mu. Mol/L, three wells per group. Incubation for 24h, discarding old culture solution, washing with PBS for 2 times, incubating with AO-EB working solution for 5-15min, washing with PBS for 2 times, and observing cell morphology and color under a fluorescence microscope.
3.1.2 experimental results
We found through AO-EB fluorescence double staining experiments that cells became round, shrunken, less intercellular adhesion, and emitted stronger green fluorescence (early apoptotic cells) after 12-ODPXA treatment compared to the control group, while late apoptotic cells increased with increasing dose (orange color). The experimental result is shown in figure 6.
3.2 Annexin V-FITC and PI apoptosis fluorescent staining
3.2.1 Experimental methods
SKOV3 cells with good growth status were cultured at 1.5X10 5 The cells/wells were spread evenly in 6-well plates at 37℃with 5% CO 2 Is cultured in a constant temperature cell incubator. After 24h incubation, 12-ODPXA diluted in complete medium was added to give final concentrations of 0. Mu. Mol/L (control), 2. Mu. Mol/L, 4. Mu. Mol/L, 8. Mu. Mol/L, three wells per group. After 48h of drug treatment, the old culture broth was discarded, cells were digested with pancreatin without EDTA, complete medium was added to terminate digestion, cells were harvested in flow tubes and centrifuged at 1500r/min for 5min, and the supernatant was discarded. The cells were washed 2 times with PBS and centrifuged at 1500r/min for 5min. Cells were then resuspended in 300. Mu.l of 1 Xbinding Buffer, 2. Mu.l of Annexin V-FITC were added to each tube and incubated for 20min in the dark. Then 2 μl Propidium Iodide (PI) was added to each tube, and the assay was performed with a flow cytometer, and finally the data was processed and analyzed with FlowJo 7.
3.2.2 experimental results
The experimental results are shown in Table 8 and figure 7, and the flow type experiment shows that the proportion of apoptotic cells in SKOV3 cells is obviously increased after the 12-ODPXA dry state with different concentrations, and the apoptosis of the SKOV3 cells is induced by the 12-ODPXA in a dose-dependent manner.
TABLE 8 influence of 12-ODPXA on SKOV3 apoptosis Rate
Western blot experiment
4.1 Experimental methods
4.1.1 preparation of protein samples
The SKOV3 cells with good growth state are evenly spread in a cell culture dish at a proper density at 37 ℃ and 5% CO 2 Is cultured overnight in a constant temperature cell incubator. When the cell density reaches about 70%, adding 12-ODPXA diluted by complete culture medium to make the final concentration be respectively 0 μmol/L (control group), 2 μmol/L, 4 μmol/L and 8 μmol/L, adding medicine for 24 hr, collecting cells in the culture dish in 1.5ml EP tube by using cell scraper, centrifuging for 5min at 1500r/min, washing with PBSAnd (3) adding a proper amount of RIPA lysate containing the protease inhibitor into each tube, fully and uniformly mixing, and standing on ice for 30min. Then, the supernatant was centrifuged at 12000r/min at 4℃for 10min, and the protein concentration was measured by pipetting, and protein quantification was performed by adding PBS and 6×loading Buffer. Mixing, decocting in metal bath at 95deg.C for 5min, cooling, and storing in refrigerator at-80deg.C.
4.1.2 electrophoresis
Cleaning a glass plate, airing, fixing the glass plate, preparing separating gel and concentrated gel with corresponding concentrations according to the molecular weight of protein to be run and the specification of a gel preparation kit, slowly adding the separating gel between the glass plates, sealing with absolute ethyl alcohol, discarding the absolute ethyl alcohol after the separating gel is solidified, adding the concentrated gel, immediately and slowly inserting a comb above the separating gel vertically, standing for gelation, assembling the separating gel and an electrophoresis device, pouring electrophoresis liquid into an electrophoresis tank, slowly pulling out the comb in parallel, adding a sample by a sample adder, sequentially adding maker 2 mu L, and preparing a protein sample (the protein content of each hole is kept between 20 mu g and 40 mu g). The power is turned on, the electrophoresis is set to 80V at the beginning, after the marker enters the separation gel, the voltage is adjusted to 120V, and the electrophoresis time is adjusted according to the target protein.
4.1.3 transferring film and sealing electrophoresis, taking out electrophoresis gel, putting into transferring film liquid, cutting gel without target protein, cutting PVDF film with corresponding size according to size of gel, activating PVDF film with methanol for 2-3min, putting into transferring film groove according to sequence of positive pole sponge, filter paper, PVDF film, gel, filter paper and negative pole sponge on clamping plate, simultaneously adding a small volume ice bag into groove, pouring transferring film liquid, adjusting transferring film time and current according to molecular weight of target protein, connecting power supply, putting transferring film groove into ice transferring film. After the membrane transfer is completed, the PVDF membrane is taken out and put into a sealing liquid for sealing, and the shaking table is used for sealing for 1.5 hours at room temperature.
4.1.4 incubation of primary and secondary antibodies
Primary antibodies (Bcl-2, bax, MMP-2, MMP-9, vimentin, N-cadherein, etc.) were diluted according to the instructions and incubated overnight on a shaker at 4 ℃. The PVDF membrane was lightly washed three times with TBST for a period of 8min each on a shaker. The fluorescent secondary antibodies were diluted with TBST according to the ratio of the instructions, incubated for 0.5-1h at room temperature, washed three times with TBST for 5min each.
4.1.5 development
The data were stored by development with a developing instrument.
4.2 experimental results
Western blot experiment results show that the 12-ODPXA dry prognosis can influence the migration and invasion of SKOV3 cells and the expression level of EMT-related proteins, such as down-regulating protein expression of MMP-2, MMP-9, vimentin and N-Cadherin. The 12-ODPXA treatment can also regulate the expression level of protein related to apoptosis of SKOV3 cells, wherein the expression of the pro-apoptotic protein Bax can be up-regulated, and the expression of the apoptotic protein Bcl-2 can be down-regulated. The effect of 12-ODPXA on the expression level of ovarian cancer SKOV3 cell MMP-2, MMP-9, vimentin and N-Cadherin, bax, bcl-2 proteins is shown in figure 8.
Example 2
Application of 12-O-deacetyl-photomoxanthone A in preparation of anti-ovarian cancer drugs, wherein the chemical structural formula of the compound 12-O-deacetyl-photomoxanthone A is as follows:
the compound 12-O-deacetyl-phomoxantone A is singly or additionally provided with one or more pharmaceutically acceptable carriers or auxiliary materials to prepare a clinically acceptable pharmaceutical preparation for treating ovarian cancer; the anti-ovarian cancer drug is a drug for inhibiting proliferation of ovarian cancer cells and/or promoting apoptosis of ovarian cancer cells.
Claims (3)
1.12-OApplication of deacetyl-phomoxantrone A in preparation of anti-ovarian cancer drugs, compound 12-OThe formula of the deacetyl-photomoxanthone a is: c (C) 36 H 36 O 15 The chemical structural formula is as follows:
2. the use according to claim 1, characterized in thatThe compound 12-OThe deacetyl-phomoxantrone A is used for preparing a clinically acceptable pharmaceutical preparation for treating ovarian cancer by singly or additionally adding one or more pharmaceutically acceptable carriers or auxiliary materials.
3. The use according to claim 1, wherein the anti-ovarian cancer drug is a drug that inhibits proliferation of ovarian cancer cells and/or promotes apoptosis of ovarian cancer cells.
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