CN104224815A - Application of solasodine in preparing antitumor drug - Google Patents
Application of solasodine in preparing antitumor drug Download PDFInfo
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- CN104224815A CN104224815A CN201310240958.3A CN201310240958A CN104224815A CN 104224815 A CN104224815 A CN 104224815A CN 201310240958 A CN201310240958 A CN 201310240958A CN 104224815 A CN104224815 A CN 104224815A
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Abstract
The invention belongs to the field of medicines, relates to application of solasodine in preparing an antitumor drug and particularly relates to application of solasodine in preparing a drug-resistant reversal agent of an antitumor drug. The solasodine is a natural product which has effect of reversing multidrug resistance of tumor cells, and can be used as a reversal agent for multidrug resistance of tumors. The solasodine further has effects of increasing sensitivity of tumor multidrug-resistant cells on the anti-tumor drug and can be used as a chemosensitizer. The invention further provides a method for inhibiting tumor multidrug-resistant cell multiplication by a pharmaceutical composition that combines the anti-tumor drug and solasodine. According to the invention, a small molecule compound solasodine can be used as a novel antitumor drug or an auxiliary ingredient thereof to be developed, and is obvious in tumor inhibiting effect, green and environment-friendly, so that a new way and means is provided for treating and curing tumors.
Description
Technical field
The invention belongs to medicine, relate to reverse multiple drug resistance of tumor and enhanced sensitivity antitumor drug, be specifically related to the application of solasodine in preparation tumor multiple medicines inversion agent and antitumor drug sensitizer.
Background technology
The life and health of the malignant tumor serious harm mankind, has become the lethal one of the main reasons of dying of current disease.The essential therapeutic arsenals of current malignant tumor has operative treatment, radiation and chemotherapy etc.For being diagnosed as the patient of late tumor and the patient of transfer having occurred, chemotherapy is one and selects preferably.Clinician obtains maximum curative effect and minimum toxicity by regulating dosage to optimize, and helps patient extend life span and improve prognosis quality of life.But the generation of the drug resistance of tumor cell causes tumor cell to decline to the sensitivity of chemotherapeutics, greatly limit the treatment of chemotherapy effect [Dean, M., T. Fojo, and S. Bates,
tumour stem cells and drug resistance.nat Rev Cancer, 2005.
5(4): p. 275-84.].Tumor cell is to after certain drug resistant, can to the raw crossing drug resistant of never contacted, that structure different, mechanism of action is different Treated with Chemotherapeutic Drugs produce, this phenomenon is called the multidrug resistance (Multiple Drug Resistance, MDR) of tumor.The generation of multidrug resistance be one of great difficult problem faced of current cancer therapies [H, L.,
an overview of cancer multidrug resistance: a still unsolved problem.cell. Mol. Life Sci., 2008.
65: p. 3145 – 3167. Mellor, H.R. and R. Callaghan,
resistance to chemotherapy in cancer:a complex and integrated cellular response.pharmacology, 2008.
81(4): p. 275-300. Mimeault, M., R. Hauke, and S. Batra,
recent Advances on the Molecular Mechanisms Involved in the Drug Resistance of Cancer Cells and Novel Targeting Therapies.clin Pharmacol Ther., 2008.
83: p. 673 – 691.].MDR, once produce, is invalid by strengthening drug dose, can produce stronger toxicity and further inducibly resistant generation [Akan, I., et al.,
n-acetylcysteine enhances multidrug resistance-associated protein 1 mediated doxorubicin resistance.eur J Clin Invest, 2004.
34(10): p. 683-9. Akan, I., et al.,
multidrug resistance-associated protein 1 (MRP1) mediated vincristine resistance:effects of N-acetylcysteine and Buthionine sulfoximine.cancer Cell Int, 2005.
5(1): p. 22. Choi, C.H.,
aBC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal.cancer Cell Int, 2005.
5: p. 30. Liscovitch, M. and Y. Lavie,
cancer multidrug resistance:a review of recent drug discovery research.iDrugs, 2002.
5(4): p. 349-55.].Most medicine relevant with MDR is all hydrophobicity or amphipathic natural product, as taxanes, anthracycline antibiotics, vinca alkaloids etc. [Choi, C.H.,
aBC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal.cancer Cell Int, 2005.
5: p. 30., Ambudkar, S.V., et al.,
biochemical, cellular, and pharmacological aspects of the multidrug transporter.annu Rev Pharmacol Toxicol, 1999.
39: p. 361-98. Krishna, R. and L.D. Mayer,
multidrug resistance (MDR) in cancer. Mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the pharmacokinetics of anticancer drugs.eur J Pharm Sci, 2000.
11(4): p. 265-83.].The generation of MDR has number of mechanisms, comprise the minimizing that cell absorbs some water soluble drugs, the change of cell cycle, the enhancing of DNA repair function, the apoptosis of T suppression cell, medicine in the change of intracellular metabolic process, to hydrophobic drug and the [Stavrovskaya such as increase being easy to some drug effluxes entering cell, A.A.
cellular mechanisms of multidrug resistance of tumor cells.biochemistry (Mosc), 2000. 65 (1): p. 95-106.].The forming process of tumor MDR is complicated, and these resistance mechanisms often exist simultaneously, but based on a kind of mechanism, interacts between different mechanisms, may work alone or in combination [Szakacs, G., et al.,
targeting multidrug resistance in cancer.nat Rev Drug Discov, 2006. 5 (3): p. 219-34].
In order to overcome the MDR characteristic of tumor cell to chemotherapeutics, researcheres are finding the inhibitor of effective abc transport albumen always, these compounds are otherwise known as the inhibitor of MDR, regulator, inversion agent or chemotherapeutic sensitizer, they can regulate the function [Choi of multiple abc transport albumen usually, C.H.
aBC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal.cancer Cell Int, 2005.
5: p. 30. Liscovitch, M. and Y. Lavie,
cancer multidrug resistance:a review of recent drug discovery research.iDrugs, 2002.
5(4): p. 349-55.].1981, Tsuruo reported first calcium channel blocker verapamil (Verapamil) and pherylarsin oxide trifluoperazine (TFP) all can strengthen tolerant mice leukemia P388/VCR cell to vincristine (vincristine in testing in vitro and in vivo, VCR) sensitivity [Ozben, T.
mechanisms and strategies to overcome multiple drug resistance in cancer.fEBS Lett, 2006. 580 (12): p. 2903-9.].In the research of 30 years subsequently, being constantly found and studying of new MDR reversal agents, but higher cytotoxicity is a large problem of puzzlement MDR inhibitor research and development always.Therefore, the MDR inhibitor that exploitation toxicity is less, reverse effect is stronger or inversion agent remain one of focus of tumour medicine research.
In the research process of MDR inhibitor of new generation, the MDR reversal agents of screening high-efficiency low-toxicity from natural product day by day pay attention to by medical circle and become the focus of research gradually.Multiple natural product is found to have the effect of reversing tumor cell MDR.
Solasodine (solasodine, 1), has another name called solasodine; Qie Xie Alkaline; Solasodine; Australian eggplant ammonium; Australian eggplant ammonium; Solasodine is a kind of important steroid alkaloid, extracts and obtain from the green fruit of nightshade (Solanum sodomeum).Its relevant parameter is as follows:
No. CAS: 126-17-0
English name: SOLASODINE
English synonym: Solasodin; Salasdine; Nsc178260; Salasodine; Sosasodine;
SOLASODINE;Solanidine-S;PURAPURIDINE;SOLANCARPIDINE;Spirosol-5-en-3-ol
CBNumber:CB5132193
Molecular formula: C27H43NO2
Molecular weight: 413.64
Structure is as follows:
Solasodine is present in about 250 kinds of nightshades.In China, solasodine is mainly present in the herb of the raw fruit of Australian eggplant, the fruit of Fructus Solani Dulcamarae, Herba Solani Lyrati and Herba Solani Nigri.
Solasodine can extract from above-mentioned plant, also can pass through chemosynthesis.Zhou Qinyin provides a kind of method (investigation of Herba Solani Nigri total alkaloids extracting method, contemporary medical science 2007.10 total 127th phase) extracting solasodine from Herba Solani Nigri.
About solasodine, to the adjustment of tumor cell drug resistance, there is not been reported at present.
Summary of the invention
The object of this invention is to provide the novelty teabag of a kind of micromolecular compound solasodine in pharmacy, namely the novelty teabag in multidrug resistance reversing agent prepared by solasodine.
Another object of the present invention is to the application of the antineoplastic pharmaceutical compositions of providing package containing the antitumor drug such as solasodine and VCR and ADR in the medicine of preparation treatment multidrug resistance of tumor.
The invention provides solasodine and preparing the application in antitumor drug, described application is the application of solasodine in the reversal agent of drug resistance preparing antitumor drug.
Wherein, solasodine can be multidrug resistance reversing agent.
Described tumor comprises oral cancer, breast carcinoma, hepatocarcinoma, pulmonary carcinoma, cervical cancer, adenocarcinoma of lung, colon cancer or cancer of pancreas.
Described antitumor drug is vincristine, daunorubicin, paclitaxel or 5-fluorouracil.
Solasodine also can be the sensitizer of antitumor drug.
Present invention also offers a kind of antineoplastic pharmaceutical compositions, the effective ingredient of described antineoplastic pharmaceutical compositions is antitumor drug and solasodine.
Described antitumor drug is cell cycle specific agents or cell cycle nonspecific agent (CCNSA).
Described antitumor drug is vincristine, daunorubicin, paclitaxel or 5-fluorouracil.
Present invention also offers a kind of method impelling external cells of resistant tumors enhanced sensitivity, namely in the culture medium of cells of resistant tumors, add solasodine.
Described tumor comprises oral cancer, breast carcinoma, hepatocarcinoma, pulmonary carcinoma, cervical cancer, adenocarcinoma of lung or cancer of pancreas.
The invention provides solasodine and prepare the application in antitumor drug.Solasodine is natural product, can the propagation of obvious inhibition tumor cell when high dose.Experiment shows, solasodine obviously can overcome the drug resistance of multidrug resistance cell KB/VCR and MCF-7/ADR, the resistant characterization of reverse multiple drug resistance of tumor cell, strengthens chemotherapeutics to the therapeutic effect of cells of resistant tumors.Micromolecular compound of the present invention is developed as new antitumor drug or its auxiliary element, and tumor killing effect is obvious, environmental protection, provides a kind of new approach and means by for treatment and healing tumor.
Detailed description of the invention
The cytotoxicity of solasodine is less, to the IC of kinds of tumor cells
50all be greater than 40 μMs, there is good safety.The present invention, by random screening, finds that this natural product has the effect of reversion MDR.In view of the efficient feature of its low toxicity, have a good application prospect.Experiment shows, solasodine can strengthen the inhibition that chemotherapeutics is bred tumor multi-medicine drug-resistant cell strain, the effect of reverse multidrug drug resistance.Such as, show in embodiment, solasodine can reverse the drug-resistant effect of KB/VCR cell to VCR, strengthens KB/VCR cell to the sensitivity of chemotherapeutics VCR, promotes that VCR is to the inducing action of the apoptosis of KB/VCR cell.Solasodine significantly can overcome the drug resistance of multidrug resistance cell KB/VCR and MCF-7/ADR, the multidrug resistance characteristic of reversing tumor cell, strengthens chemotherapeutics to the therapeutic effect of tumor multi-medicine drug-resistant tumor cell.
Micromolecular compound solasodine of the present invention is purchased from institute of materia medica of the Chinese Academy of Sciences, and high performance liquid chromatography surveys purity, HPLC >=98%.Its structure is as follows:
The invention provides solasodine and prepare the application in multidrug resistance reversing agent (Reversal agent).
Described tumor can be the various tumors such as oral cancer, breast carcinoma, hepatocarcinoma, pulmonary carcinoma, cervical cancer or cancer of pancreas to chemotherapeutics generation drug resistance.Described tumor cell can be the tumor cell of oral cancer, breast carcinoma, hepatocarcinoma or cervical cancer to chemotherapeutics generation drug resistance.Such as, multidrug resistance cell KB/VCR and MCF-7/ADR adopted in embodiment.
Described antitumor drug can be medicines resistant to liver cancer, anti-oral cancer medicine or Antilung gland cancer medicine, can be cell cycle specific agents (CCSA), as vincristine, paclitaxel etc., it also can be the cell cycle nonspecific agent (CCNSA) such as daunorubicin, 5-fluorouracil (CCNSA).
Described antitumor drug reversal agent of drug resistance can be made into the pharmaceutically acceptable dosage form of any one, comprises tablet, capsule, granule, oral liquid, slow releasing preparation, controlled release preparation, nanometer formulation, injection etc.
Present invention also offers the application of solasodine in the sensitizer (sensitizer) preparing antitumor drug.
Solasodine can overcome the resistant characterization of tumor multi-medicine drug-resistant cell, and increase tumor drug resistance cell to the sensitivity of medicine, the enhancing G2/M phase of VCR to the multidrug resistance cell caused by the apoptosis-promoting effect of KB/VCR cell and ADR blocks.
The reversal agent of drug resistance of the antitumor drug described in the present invention or the active component of sensitizer are solasodines.
Present invention also offers a kind of antineoplastic pharmaceutical compositions, said composition comprises solasodine and antitumor drug.Described antitumor drug can be the cell cycle specific agents such as vincristine, paclitaxel (CCSA), also can be the cell cycle nonspecific agent (CCNSA) such as daunorubicin, 5-fluorouracil (CCNSA).Solasodine also can with surgical operation conbined usage, with one or more Western medicine conbined usage, with Chinese herbal medicine conbined usage, with radiation treatment conbined usage.
On the other hand, the invention provides a kind of method of multidrug resistance tumor cells to chemotherapy drug susceptibility increasing In vitro culture, namely in the culture medium of multidrug resistance tumor cells, add solasodine.
Described tumor comprises oral cancer, breast carcinoma, hepatocarcinoma, pulmonary carcinoma, cervical cancer, adenocarcinoma of lung or cancer of pancreas.Described tumor cell can be the various tumor cells such as oral cancer, breast carcinoma, hepatocarcinoma, pulmonary carcinoma, cervical cancer or cancer of pancreas to chemotherapeutics generation drug resistance.Such as, multidrug resistance cell KB/VCR and MCF-7/ADR adopted in embodiment.
After tumor cell dosing, in culture medium, the concentration of solasodine can be greater than 20 μMs, is even greater than 50 μMs.But, even if the concentration of solasodine is lower in culture medium, such as 10-20 μM, even close to but when not comprising 0 μM, solasodine still can play the effect of multidrug resistance reversing agent or chemotherapeutic sensitizer.
Micromolecular compound solasodine of the present invention can adopt the preparation method of various routine to prepare.Such as, the method can synthesized from separation and purification in plant (such as, the green fruit of nightshade) or artificial chemistry.
Utilize micromolecular compound of the present invention, by various conventional screening assays, can filter out, with solasodine, interactional material occur, as receptor, inhibitor or antagonist etc.
The present invention and inhibitor, antagonist etc., when carrying out using (administration) on treating, can provide different effects.Usually, but these materials are formulated in nontoxic, inertia with in pharmaceutically acceptable aqueous carrier medium, wherein pH is about 5-8 usually, and preferably pH is about 6-8, although pH value can with being formulated the character of material and disease to be treated and changing to some extent.The pharmaceutical composition prepared can carry out administration by conventional route, comprising (but being not limited to): intramuscular, intraperitoneal, subcutaneous, Intradermal or topical.
For solasodine of the present invention, can by itself and suitable pharmaceutically acceptable carrier coupling.This kind of pharmaceutical composition contains the compound and pharmaceutically acceptable carrier or excipient for the treatment of effective dose.This kind of carrier comprises (but being not limited to): normal saline, buffer, glucose, water, glycerol, ethanol and combination thereof.Pharmaceutical preparation should match with administering mode.Solasodine of the present invention can be made into injection form, such as, be prepared by conventional method with normal saline or the aqueous solution containing glucose and other adjuvant.The pharmaceutical composition of such as Tablet and Capsula and so on, is prepared by conventional method.Pharmaceutical composition such as injection, solution, Tablet and Capsula should aseptically manufacture.The dosage of active component is treatment effective dose, such as every day about 1 microgram/kg body weight-Yue 5 mg/kg body weight.In addition, solasodine of the present invention also can use together with other treatment agent.
When solasodine of the present invention is used as medicine, the solasodine for the treatment of effective dose can be applied to mammal, wherein this treatment effective dose is usually at least about 10 micrograms/kg body weight, and be in most of the cases no more than about 8 mg/kg body weight, preferably dosage is about 10 micrograms/kg body weight ~ 1 mg/kg body weight.Certainly, concrete dosage also should consider the factor such as route of administration, patient health situation, and these are all within skilled practitioners skill.
Solasodine is natural product, has certain Clinical practice and is worth.That studies the chemistry and biology of this compounds along with people gos deep into, its molecular mechanism of action will be progressively clear and definite, this will promote modifying for chemical structure and the structure activity study of this compounds further, and contribute to the medical value improving this compounds.
Below in conjunction with specific embodiment, the present invention is described further, but protection scope of the present invention is not limited in this.Should be understood that within the scope of the present invention, above-mentioned each technical characteristic of the present invention and can combining mutually between specifically described each technical characteristic in below (eg embodiment), thus form new or preferred technical scheme.As space is limited, tiredly no longer one by one to state at this.
implement 1:CCK-8 test kit and detect drug-resistant cell strain to the drug resistance multiple of solasodine
Experiment material:
Solasodine is purchased from institute of materia medica of the Chinese Academy of Sciences, and purity is not less than 98%.Human oral cancer cell strain KB and drug-resistant cell strain KB/VCR thereof provided by Chinese Academy of Sciences's medicine, MCF-7 cell strainHJ2mm/ADR and drug-resistant cell strain MCF-7/ADR thereof, human colon carcinoma HCT-8 and drug-resistant cell strain HCT-8/VCR thereof are all purchased from Nanjing Kai Ji biotech firm.Verapamil (VPL), vincristine (VCR) and amycin (ADR) are purchased from Roche chemical company, and purity is all greater than 99%.CCK-8 test kit is purchased from colleague company.
Experimental technique:
Cell recovery
1) from liquid nitrogen container, take out cryopreservation tube, directly drop in 37 DEG C of warm water, and shake makes it melt as early as possible frequently.
2) from 37 DEG C of water-baths, take out cryopreservation tube, with suction pipe sucking-off cell suspension, inject centrifuge tube and add more than 10 times culture fluid, low-speed centrifugal after mixing, abandons supernatant, then repeats to wash once with culture fluid.
3), after suitably diluting with culture fluid, inoculated and cultured bottle, be placed on 37 DEG C of incubator quiescent culture, next day changes culture fluid, continues to cultivate.Go down to posterity when being cultured to finite concentration.
Passage is cultivated
Human oral cancer cell strain KB and drug-resistant cell strain KB/VCR thereof is incubated in the α-MEM culture medium containing 10% hyclone and 1mM Sodium Pyruvate, and MCF-7 cell strainHJ2mm/ADR and drug-resistant cell strain MCF-7/ADR thereof is incubated in 1640 culture medium containing 10% hyclone.
The situation of observation of cell growth every day, when cell grows to about 90% degree of converging (attached cell) in culture bottle, goes down to posterity according to the ratio of 1:3 to 1:5, about went down to posterity once every 2 ~ 4 days.Method is as follows:
1) with 1 × phosphate buffer wash cell once.
2) add 1 ~ 2 ml 0.25% tryptic digestive juice digestion, be placed in 37 DEG C of incubator numbers minute.Pat Tissue Culture Flask with hands, make cell separation.
3) trypsinization is stopped with the suitable culture medium containing 10%Gibco hyclone.Cell is sub-packed in new culture bottle, continues to cultivate.
Cell cryopreservation
1) get the cell being cultured to exponential phase, trypsinization, to be collected in centrifuge tube and to count, centrifugal.
2) reject trypsin and old culture fluid, add the frozen culture fluid (containing 10% DMSO, 40% DMEM and 50% Gibico hyclone) configured, in cryopreserving liquid, the ultimate density of cell is 0.5-1 × 10
7/ ml.Blowing and beating gently with suction pipe makes cell even, and be then distributed in aseptic cryopreservation tube, often pipe adds 1-1.5ml.
3) cryopreservation tube is put into freezing storing box and be placed in-80 DEG C, move in liquid nitrogen container after 5 hours and preserve.
CCK-8 tests
KB and KB/VCR cell and MCF-7 and MCF-7/ADR cell are all inoculated in 96 orifice plates according to the density in 3500/ hole, the ADR of variable concentrations after 24 h, VCR, is added in each hole after solasodine and VCR and the solasodine one α-MEM reinstated containing 10% hyclone prepares.After cultivating 48 h, discard culture fluid, every hole adds 90 μ L not containing culture medium and the 10 μ L CCK-8 reagent of serum.After 37 DEG C of reaction 2 h, microplate reader reads the light absorption value (OD450) of 450 nm wavelength.By calculating the cell proliferation ratio of medication group relative to matched group.Blank group only adds culture medium for not adding cell, and matched group is add the DMSO with medicine same volume, cell survival rate=(experimental group OD450-blank group OD450)/(matched group OD450-blank group OD450).Pass through IC
50value calculates drug resistance multiple (Resistance Fold, RF) again.
The IC of RF=drug-resistant cell strain
50the IC of value/parental cell strain
50value.Each concentration establishes 3 repeating holes, experiment repetition 3 times.
All mdr cells grow 3 days before tying up to Cell suppression test in without pharmaceutical culture medium.Each numerical value is 3 independent experiment results, IC
50represent with " means standard deviation " form.VCR, vincristine; ADR, daunorubicin; RF, drug resistance multiple.
Experimental result:
KB/VCR and MCF-7/ADR is two kinds of conventional multidrug resistance cell strains, and in the present embodiment, these two kinds of cells also show the characteristic of multidrug resistance.As shown in table 1, KB/VCR cell is respectively 81.9 times and 94.4 times relative to the drug resistance multiple of KB cell to VCR and ADR, and the drug resistance multiple that MCF-7/ADR cell compares VCR and ADR with MCF-7 cell is 38.1 times and 20.9 times respectively, display experiment mdr cell used has multidrug resistance, and MDR activity is similar to the result of bibliographical information.
Solasodine is to the half-inhibition concentration IC of parental cell strain KB and MCF-7
50be respectively 223.1 μ Μ and 189.6 μ Μ, to the IC of drug-resistant cell strain KB/VCR and MCF-7/ADR
50be respectively 232.7 μ Μ and 196.4 μ Μ, between the two without difference, multidrug resistance cell strain KB/VCR and MCF-7/ADR does not show the crossing drug resistant to compound solasodine, illustrates that solasodine can escape the multidrug resistance of mdr cell.Solasodine under the concentration of 20 below μ Μ, cell growth without obvious suppression, higher than can the propagation of T suppression cell under the concentration of 100 μ Μ.
Conclusion: solasodine can overcome the drug resistance of drug-resistant cell strain, drug-resistant cell strain is substantially identical to the sensitivity of solasodine.
embodiment 2:CCK-8 method detects solasodine to the reverse effect of tumor cell multidrug resistance activity
Experiment material: with embodiment 1.
Experimental technique:
Solasodine enhanced sensitivity is tested: KB/VCR, MCF-7/ADR and HCT-8/VCR cell is inoculated in 96 orifice plates according to the density in 3500/ hole, the VCR of variable concentrations after 24 h, and the VCR of variable concentrations and the solasodine one α-MEM reinstated containing 10% hyclone prepare after be added in each hole.After cultivating 48 h, discard culture fluid, with method in embodiment 1, survey drug-resistant cell strain and parental cell thereof to the activity of VCR and VCR+ solasodine with CCK-8 test kit, plot curve.Each concentration establishes 3 repeating holes, experiment repetition 3 times.
Experimental result:
The drug resistance multiple of KB/VCR cell to VCR is 81.9 times, and the drug resistance multiple of MCF-7/ADR to ADR is 20.9 times.After adding the solasodine of 20 μMs, make the sensitivity of KB/VCR cell to VCR add 2.1 times, and the sensitivity of ADR to mdr cell MCF-7/ADR add 3.3 times.Solasodine can reverse multiple drug resistance of tumor cell to the drug resistance of chemotherapeutics.And this effect shows in parental cell and not obvious.
Conclusion:
Solasodine can the drug resistance of reverse multiple drug resistance of tumor cell KB/VCR and MCF-7/ADR.
The all documents mentioned in the present invention are quoted as a reference all in this application, are just quoted separately as a reference as each section of document.In addition should be understood that those skilled in the art can make various changes or modifications the present invention after having read above-mentioned teachings of the present invention, these equivalent form of values fall within the application's appended claims limited range equally.
Claims (10)
1. the application in antitumor drug prepared by the solasodine of following formula structure, and described application is the application of solasodine in the reversal agent of drug resistance preparing antitumor drug,
。
2. apply as claimed in claim 1, it is characterized in that, solasodine is multidrug resistance reversing agent.
3. apply as claimed in claim 1, it is characterized in that, described tumor comprises oral cancer, breast carcinoma, hepatocarcinoma, pulmonary carcinoma, cervical cancer, adenocarcinoma of lung, colon cancer or cancer of pancreas.
4. apply as claimed in claim 1, it is characterized in that, described antitumor drug is vincristine, daunorubicin, paclitaxel or 5-fluorouracil.
5. apply as claimed in claim 1, it is characterized in that, solasodine is the sensitizer of antitumor drug.
6. an antineoplastic pharmaceutical compositions, is characterized in that, the effective ingredient of described antineoplastic pharmaceutical compositions is antitumor drug and solasodine.
7. antineoplastic pharmaceutical compositions as claimed in claim 6, it is characterized in that, described antitumor drug is cell cycle specific agents or cell cycle nonspecific agent (CCNSA).
8. antineoplastic pharmaceutical compositions as claimed in claim 6, it is characterized in that, described antitumor drug is vincristine, daunorubicin, paclitaxel or 5-fluorouracil.
9. impel a method for external cells of resistant tumors enhanced sensitivity, it is characterized in that, in the culture medium of cells of resistant tumors, add solasodine.
10. method as claimed in claim 9, it is characterized in that, described tumor comprises oral cancer, breast carcinoma, hepatocarcinoma, pulmonary carcinoma, cervical cancer, adenocarcinoma of lung or cancer of pancreas.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111714502A (en) * | 2020-07-09 | 2020-09-29 | 中国水产科学研究院长江水产研究所 | Application of solasodine in preparing medicine for killing fish ectoparasite |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1274445B1 (en) * | 1999-12-30 | 2005-09-14 | YEDA RESEARCH AND DEVELOPMENT Co. LTD. | Use of steroidal alkaloids to reverse multidrug resistance |
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2013
- 2013-06-18 CN CN201310240958.3A patent/CN104224815A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1274445B1 (en) * | 1999-12-30 | 2005-09-14 | YEDA RESEARCH AND DEVELOPMENT Co. LTD. | Use of steroidal alkaloids to reverse multidrug resistance |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111714502A (en) * | 2020-07-09 | 2020-09-29 | 中国水产科学研究院长江水产研究所 | Application of solasodine in preparing medicine for killing fish ectoparasite |
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Application publication date: 20141224 |