CN117159545A - Application of pitchon in preparation of ovarian cancer treatment medicine - Google Patents
Application of pitchon in preparation of ovarian cancer treatment medicine Download PDFInfo
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- CN117159545A CN117159545A CN202311155699.4A CN202311155699A CN117159545A CN 117159545 A CN117159545 A CN 117159545A CN 202311155699 A CN202311155699 A CN 202311155699A CN 117159545 A CN117159545 A CN 117159545A
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- ovarian cancer
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- 206010033128 Ovarian cancer Diseases 0.000 title claims abstract description 52
- 206010061535 Ovarian neoplasm Diseases 0.000 title claims abstract description 52
- 239000003814 drug Substances 0.000 title claims abstract description 27
- 230000000694 effects Effects 0.000 claims abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
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- 230000002708 enhancing effect Effects 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 12
- 230000006907 apoptotic process Effects 0.000 abstract description 7
- 230000035755 proliferation Effects 0.000 abstract description 4
- 238000011160 research Methods 0.000 abstract description 3
- 239000003560 cancer drug Substances 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 32
- 230000003833 cell viability Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 108010040476 FITC-annexin A5 Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000003698 anagen phase Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
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- 238000002835 absorbance Methods 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000006882 induction of apoptosis Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- PEZPMAYDXJQYRV-UHFFFAOYSA-N pixantrone Chemical compound O=C1C2=CN=CC=C2C(=O)C2=C1C(NCCN)=CC=C2NCCN PEZPMAYDXJQYRV-UHFFFAOYSA-N 0.000 description 2
- 229960004403 pixantrone Drugs 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- OIIMUKXVVLRCAF-UHFFFAOYSA-N 10-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dien-1-yl)decyl-triphenylphosphanium Chemical class O=C1C(OC)=C(OC)C(=O)C(CCCCCCCCCC[P+](C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1C OIIMUKXVVLRCAF-UHFFFAOYSA-N 0.000 description 1
- 208000028564 B-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 102400000888 Cholecystokinin-8 Human genes 0.000 description 1
- 101800005151 Cholecystokinin-8 Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000012661 PARP inhibitor Substances 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 241000244269 Peucedanum Species 0.000 description 1
- 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000007537 Type II DNA Topoisomerases Human genes 0.000 description 1
- 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 1
- 229940124532 absorption promoter Drugs 0.000 description 1
- -1 absorption promoters Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
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- 239000011230 binding agent Substances 0.000 description 1
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- 230000009702 cancer cell proliferation Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
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- 239000002547 new drug Substances 0.000 description 1
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- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
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- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The application relates to the technical field of medicines, in particular to application of pitaxetron in preparation of medicines for treating ovarian cancer. According to the application, the research discovers that the pitchon can obviously inhibit the activity and proliferation of ovarian cancer drug-resistant cell strain SKOV3 and non-drug-resistant cell strain A2780 for the first time; and can induce apoptosis of ovarian cancer cells. The experimental evidence of the application shows that the pitchotron has good anti-ovarian cancer effect, is hopeful to be developed into a novel and efficient medicine for treating ovarian cancer, on one hand, the novel application of the pitchotron is developed, and on the other hand, a novel medicine is provided for treating ovarian cancer.
Description
Technical Field
The application relates to the technical field of medicines, in particular to application of pitaxetron in preparation of medicines for treating ovarian cancer.
Background
Ovarian cancer is a common malignancy of the female reproductive system, and in recent years, the incidence and mortality rate of ovarian cancer have increased. Since ovarian cancer is usually free from obvious symptoms in early stage, most patients are already in late stage when diagnosis is carried out, and the treatment difficulty is high. At present, the treatment of the ovarian cancer mainly adopts a comprehensive treatment method of surgery and chemotherapy, and the survival rate of patients with the ovarian cancer is obviously improved along with the continuous progress of surgical operation technology and the continuous updating of chemotherapy drugs. The platinum-based combined chemotherapy is a first-line chemotherapy scheme of the current ovarian cancer, and although the platinum-based chemotherapy has good curative effect on the ovarian cancer, the survival rate of ovarian cancer patients is seriously affected by the problems of platinum resistance or recurrence after treatment, so that the survival rate of middle-late stage ovarian cancer patients is less than 30% in 5 years. Therefore, there is no choice in developing a new drug for treating ovarian cancer.
Pixantrone (Pixantrone) of formula C 17 H 19 N 5 O 2 The molecular weight is 325.37. The pitaxadiol is a derivative of mitoquinone, belongs to an azaanthracene dione antitumor drug, has a similar action mechanism to Mi Tuoen, can be embedded into DNA of cells, and can inhibit DNA topoisomerase II, thereby playing an antitumor role. Clinically, petarone is approved for the treatment of adult recurrent or refractory aggressive non-hodgkin B-cell lymphomas. At present, the relation between the pitchoosetron and the ovarian cancer is not reported yet.
Disclosure of Invention
The application aims to provide the application of the pitchon as the medicine for treating the ovarian cancer, which not only explores the new application of the pitchon, but also provides a new medicine for treating the ovarian cancer.
In a first aspect, the application provides the use of pitchon in the manufacture of a medicament for the treatment of ovarian cancer.
In a second aspect, the application provides the use of pitchon in the manufacture of a medicament for inhibiting viability of ovarian cancer cells.
Further, the ovarian cancer cells are A2780 cells and SKOV3 cells.
According to the research, the application discovers that the pitchon can obviously inhibit the activity of ovarian cancer cells from different sources, can inhibit the proliferation of the ovarian cancer cells and induce the apoptosis of the ovarian cancer cells; proved by the experiment, the pitchon has good anti-ovarian cancer effect and is hopeful to be developed into a novel medicine for efficiently treating ovarian cancer.
In a third aspect of the present application, there is provided an anti-ovarian pharmaceutical composition comprising pitaxron as a major active ingredient.
Further, the pharmaceutical composition also comprises other effective components with therapeutic effects or enhanced therapeutic effects, reduced toxic and side effects and prolonged metabolism time.
Further, the pharmaceutical composition can also comprise other effective components for treating ovarian cancer, such as cisplatin, paclitaxel, PARP inhibitor, etc.
Further, the pharmaceutical composition also comprises pharmaceutically acceptable carriers and/or auxiliary materials.
Further, the pharmaceutically acceptable auxiliary materials comprise one or more than two of diluents, excipients, fillers, binders, wetting agents, disintegrants, absorption promoters, surfactants, adsorption carriers, lubricants, flavoring agents and sweeteners.
Furthermore, the dosage forms of the pharmaceutical composition are various forms such as tablets, powder, granules, capsules, oral liquid or injection, and the medicaments of the various dosage forms can be prepared according to a conventional method in the pharmaceutical field.
The application has the advantages that:
according to the application, the research discovers that the pitchon can obviously inhibit the activity and proliferation of ovarian cancer drug-resistant cell strain SKOV3 and non-drug-resistant cell strain A2780 for the first time; and can induce apoptosis of ovarian cancer cells. The experimental evidence of the application shows that the pitchotron has good anti-ovarian cancer effect, is hopeful to be developed into a novel and efficient medicine for treating ovarian cancer, on one hand, the novel application of the pitchotron is developed, and on the other hand, a novel medicine is provided for treating ovarian cancer.
Drawings
FIG. 1. Inhibition of ovarian cancer cell A2780 and SKOV3 viability by pitaxron;
FIG. 2 inhibition of proliferation potency of ovarian cancer cells A2780 and SKOV3 by pitaxron;
FIG. 3. Effects of Peucedanum on induction of apoptosis in ovarian cancer cells A2780 and SKOV 3.
Detailed Description
The following provides a detailed description of embodiments of the present application with reference to examples. The description of these embodiments is provided to assist understanding of the present application, but is not intended to limit the present application. In addition, the technical features of the embodiments of the present application described below may be combined with each other as long as they do not collide with each other. The following experimental methods, unless otherwise specified, are conventional, and the experimental materials used in the following experiments, unless otherwise specified, are commercially available.
Example 1: inhibition of ovarian cancer cell viability by pitchon
Ovarian cancer cells A2780 and SKOV3 in the logarithmic growth phase were inoculated into 96-well plates with 5000 cells per well and 200. Mu.L of RPMI-1640 medium. The drug treatment group, the control group and the blank group are respectively arranged. Wherein, the drug treatment group is a group containing the pitchon with different concentrations, the control group only contains cells without adding drugs, and the blank group does not contain cells and only contains culture medium. The drug treatment group treated cells with the drug for 24h and 48h, 4h before the end of treatment, added 20 μl CCK8 solution per well and cultured for 4h. The absorbance values were then read at a wavelength of 450nm using a multifunctional microplate reader and cell viability was calculated from the absorbance values according to the following formula:
cell viability= (drug treatment OD value-blank OD value)/(control OD value-blank OD value) ×100%. Wherein, the half-inhibitory solubility (IC 50) of cell viability was calculated using Graphpad software.
The results indicate that pitaxenic can inhibit the viability of ovarian cancer cells (fig. 1).
Example 2: inhibition of ovarian cancer cell proliferation potency by pitchon
Ovarian cancer cells A2780 and SKOV3 in the logarithmic growth phase were inoculated into six well plates with 500 cells per well and 200. Mu.L of medium. Cells were treated with different concentrations of pitchon for 9 days after complete cell attachment. The medium was changed every 3 days during the process. After the treatment was completed, the medium was discarded, washed 2 times with PBS, and fixed with ice-bath methanol for 5min and stained with crystal violet.
The results show that pitaxetron can inhibit the proliferative capacity of ovarian cancer cells (fig. 2).
Example 3: induction of apoptosis of ovarian cancer cells by pitchon
Ovarian cancer cells A2780 and SKOV in the logarithmic growth phase were treated with pitaxeron at different concentrations for 48h, and then digested with EDTA-free trypsin for 2min to single cells, centrifuged at 2000rpm for 5min after digestion, and washed 2 times with PBS. Then, the apoptosis detection kit working solution (500. Mu.L binding buffer, 5. Mu.L Annexin V-FITC dye and 5. Mu.L PI dye) was added to the cells, and the mixture was stirred and mixed uniformly, and then the mixture was left to react in the dark for 15min. The proportion of apoptosis was measured by flow cytometry. Wherein, the cells of Annexin V-FITC single positive and Annexin V-FITC/PI double positive are apoptosis cells.
The results indicate that pitaxenic can induce apoptosis of ovarian cancer cells (figure 3).
While the preferred embodiments of the present application have been described in detail, the present application is not limited to the embodiments, and various equivalent modifications and substitutions can be made by those skilled in the art without departing from the spirit of the present application, and these equivalent modifications and substitutions are intended to be included in the scope of the present application as defined in the appended claims.
Claims (7)
1. Application of pitchon in preparing medicine for treating ovarian cancer is provided.
2. Application of pitchon in preparing medicine for inhibiting ovarian cancer cell activity is provided.
3. The use of claim 2, wherein the ovarian cancer cells are a2780 cells and SKOV3 cells.
4. The medicine composition for resisting the ovarian cancer is characterized by taking the pitaxron as a main active ingredient.
5. The pharmaceutical composition of claim 4, wherein the pharmaceutical composition further comprises other active ingredients having therapeutic effects or enhancing therapeutic effects, reducing toxic side effects, and prolonging metabolism time.
6. The pharmaceutical composition of claim 4, further comprising a pharmaceutically acceptable carrier and/or adjuvant.
7. The pharmaceutical composition according to claim 4, wherein the pharmaceutical composition is in the form of a tablet, powder, granule, capsule, oral liquid or injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311155699.4A CN117159545A (en) | 2023-09-08 | 2023-09-08 | Application of pitchon in preparation of ovarian cancer treatment medicine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311155699.4A CN117159545A (en) | 2023-09-08 | 2023-09-08 | Application of pitchon in preparation of ovarian cancer treatment medicine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117159545A true CN117159545A (en) | 2023-12-05 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311155699.4A Pending CN117159545A (en) | 2023-09-08 | 2023-09-08 | Application of pitchon in preparation of ovarian cancer treatment medicine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117159545A (en) |
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2023
- 2023-09-08 CN CN202311155699.4A patent/CN117159545A/en active Pending
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