CN1491653A - New use of brassinolide in reversing multiple medicine resistance of tumour cell - Google Patents
New use of brassinolide in reversing multiple medicine resistance of tumour cell Download PDFInfo
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- CN1491653A CN1491653A CNA031403182A CN03140318A CN1491653A CN 1491653 A CN1491653 A CN 1491653A CN A031403182 A CNA031403182 A CN A031403182A CN 03140318 A CN03140318 A CN 03140318A CN 1491653 A CN1491653 A CN 1491653A
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Abstract
The present invention relates to the new use of brassinolide in reversing the resistance of tumor cell to multiple medicines. Brassinolide has powerful bioactivity, is safe and non-toxic. At very low concentration, brassinolide itself has no tumor inhibiting effect and can reverse the resistance of tumor cell with high resistance to multiple medicines.
Description
[technical field]
The present invention relates to a kind of new purposes of brassinosteroid reversing tumor cell multidrug resistance.
[background technology]
The tumor cell multidrug resistance is present outstanding question, directly influences the therapeutic effect and the prognosis of tumour patient.Which medicine at present clinical still do not have really to overcome multidrug resistance.
Brassinosteroid Brassinolide (hereinafter to be referred as BL) is latest model, the bioactive plant growth regulator of tool so far, and chemical name is (22R, 23R, 24R)-2 α, 3 α, 22,23-tetrahydroxy-β-homogeneous phase-7-oxa-5 alpha-lumistane-6-ketone.Being proposed from Pollen Brassicae campestris by U.S. scientist Mitchell the seventies in last century at first, is a kind of steroidal substances, and its biological activity is strong 1000 times than the other plant growth regulator, and obvious effectiveness is promptly arranged under the extremely low concentration of 0.02-0.03PPM.It is from plant pollen, and bionical building-up process is reliable, so nontoxic.As plant stimulin have efficiently, advantage such as wide spectrum, strong stress resistance, low toxicity, safety, cause that very soon the various countries scientist notes, be described as plant the 6th hormone.The eighties is Japan before this, and China has finished bionical synthetic subsequently.Brassinosteroid contains multiple growth regulator, trace element, aminoacid, endogenous phytohormone etc.Be used for agricultural production at present.
Multidrug resistance is meant that tumor cell not only develops immunity to drugs to a cancer therapy drug, and to other structure differences, the different anticarcinogen of the mechanism of action develops immunity to drugs simultaneously.Multidrug resistance is the main cause of tumor chemical therapy failure, has a strong impact on the treatment and the prognosis of tumour patient.The relevant both at home and abroad research that overcomes the tumor cell multidrug resistance had more than 20 year, but up to now, went back the really multidrug resistance of effective reversing tumor of neither one medicine.
[summary of the invention]
The new purposes that is characterized as a kind of brassinosteroid reversing tumor cell multidrug resistance of the present invention.Brassinosteroid has very strong biological activity, and safety is nontoxic, and brassinosteroid itself is not having under the very low concentration of tumor-inhibiting action, reverses highly drug-fast tumor cell drug resistance effectively.
The present invention can develop an effective multidrug resistance inversion agent, thereby reaches the chemotherapy sensitizing effect, benefit patient, and produces economic and social benefit.
[description of drawings]
Fig. 1 is that day Feng Su is to the cumulative influence of rhodamine.
Fig. 2 is the influence of day Feng Su to topology isomerase-II (TOPO-II) catalytic activity.
Fig. 3 is that day Feng Su is to sensitive strain and persister cell P53, the influence of P21 protein expression.
[specific embodiment]
Experimental technique:
Cell strain CCRF-VCR1000 is the people T lymphoblast sample leukemia cell line of inducing MDR with vincristine (VCR), and its corresponding sensitive strain is CCRF-CEM.The drug-resistance factor of employing mtt assay mensuration CCRF-VCR1000 cell and BL effect back are to chemical sproof reverse multiple.Adopt cells were tested by flow cytometry sensitive strain, persister cell to accumulation through the fluorescent dye rhodamine 123 (Rhodamine123) of P-170 glycoprotein transhipment, and after BL handles, the change of persister cell inner dye accumulation.According to the Sulliven method, measure cell topoisomerase II (TOPO-II) catalytic activity, understand of the influence of BL effect back to the TOPO-II catalytic activity.Detect sensitive cells and mdr cell P53, the influence of P21 protein expression and BL with Western blot method.
The result:
The drug resistance of CCRF-VCR1000 cell is measured:
The CCRF-VCR1000 cell is to the IC of amycin
50Value is: 8942ng/ml, its precursor sensitive strain CCRF-CEM cell is to the IC of amycin
50Value is: 58.4ng/ml, the CCRF-VCR1000 cell is 153.1 times to the drug resistance multiple of amycin.
The CCRF-VCR1000 cell is to the IC of VP-16
50Value is: 11408ng/ml, its precursor sensitive strain CCRF-CEM cell is to the IC of VP-16
50Value is: 204.1ng/ml, the CCRF-VCR1000 cell is 55.9 times to the drug resistance multiple of VP-16.
The CCRF-VCR1000 cell is to the IC of VCR
50Value is: 36554ng/ml, its precursor sensitive strain CCRF-CEM cell is to the IC of VCR
50Value is: 4.5ng/ml, the CCRF-VCR1000 cell is 8123.1 times to the drug resistance multiple of VCR.
BL is to the cytotoxicity of CCRF-CEM cell, CCRF-VCR1000 cell:
BL is at 0.001 μ g/ml, 0.01 μ g/ml, 0.1 μ g/ml, under 1.0 μ g/ml and the 10.0 μ g/ml concentration to all acellular toxic action of CCRF-VCR1000 cell.When 100 μ g/ml concentration,, be 40.4% to the persister suppression ratio to sensitive strain cell inhibitory rate 58.9%.
BL is to the chemical sproof reverse effect of CCRF-VCR1000 cell:
BL is at 0.001 μ g/ml, 0.01 μ g/ml, and 0.1 μ g/ml makes the reversal of drug resistance of CCRF-VCR1000 cell to VCR under 1.0 μ g/ml and the 10.0 μ g/ml concentration, reverses multiple and is respectively: 4.0,4.6,7.2,7.5 and 11.6 times.
BL is to CCRF-VCR1000 cell Rhodamine123 effect of accumulation:
Under the situation of no BL, the Rhodamine123 accumulation in two hours of sensitive strain CCRF-CEM cell increases in time and gradually, the Rhodamine123 accumulation of persister CCRF-VCR1000 cell is obviously slowed down, significant difference, persister CCRF-VCR1000 cell is after 10 μ g/ml BL handle 24 hours, cells were tested by flow cytometry is the result show, Rhodamine123 increases in intracellular accumulation, draws close (Fig. 1) to the figure of sensitive strain CCRF-CEM.
BL is to the influence of sensitive strain and persister cell topoisomerase II (TOPO II) catalytic activity:
TOPO-II catalytic activity measurement result shows, persister, sensitive strain and the persister after BL handles, and three's TOPO-II catalytic activity does not all have significant difference (Fig. 2).
BL is to sensitive strain and persister cell P53, the influence of P21 protein expression:
Persister P53 expresses obviously and strengthens, and the P53 protein expression level of handling 24 hours persister cell through the BL of 10.0 μ g/ml returns to the sensitive strain level.Under this experiment condition, do not measure the proteic expression of P21 (Fig. 3).
Conclusion:
Brassinosteroid only shows to a certain degree cytotoxicity in high concentration, but under acellular malicious mass action, can effectively reverse the drug resistance of CCRF-VCR1000 to VCR.
The P glycoprotein of brassinosteroid inhibition persister CCRF-VCR1000 cell membrane effluxes medicine, and the P53 protein expression level of CCRF-VCR1000 cellular abnormality is returned near the sensitive cells level.Downward modulation to the P53 of unconventionality expression may be that brassinosteroid reverses one of multidrug resistance mechanism.
Claims (1)
1, a kind of new purposes of brassinosteroid reversing tumor cell multidrug resistance is characterized by the new purposes of brassinosteroid reversing tumor cell multidrug resistance.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03140318 CN1278689C (en) | 2003-08-28 | 2003-08-28 | New use of brassinolide in reversing multiple medicine resistance of tumour cell |
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| CN 03140318 CN1278689C (en) | 2003-08-28 | 2003-08-28 | New use of brassinolide in reversing multiple medicine resistance of tumour cell |
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| Publication Number | Publication Date |
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| CN1491653A true CN1491653A (en) | 2004-04-28 |
| CN1278689C CN1278689C (en) | 2006-10-11 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006023073A1 (en) * | 2004-07-23 | 2006-03-02 | Drebsk Comptech, Inc. | Medical uses of 24-epibrassinolide |
| CN103301136A (en) * | 2013-05-21 | 2013-09-18 | 成都旗美生物科技有限公司 | Combined medical and health-care medicine of naringenin |
| CN103877100A (en) * | 2013-05-21 | 2014-06-25 | 成都旗美生物科技有限公司 | Combined medicinal and health medicament of linolenoyl ethanolamine |
-
2003
- 2003-08-28 CN CN 03140318 patent/CN1278689C/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006023073A1 (en) * | 2004-07-23 | 2006-03-02 | Drebsk Comptech, Inc. | Medical uses of 24-epibrassinolide |
| CN103301136A (en) * | 2013-05-21 | 2013-09-18 | 成都旗美生物科技有限公司 | Combined medical and health-care medicine of naringenin |
| CN103877100A (en) * | 2013-05-21 | 2014-06-25 | 成都旗美生物科技有限公司 | Combined medicinal and health medicament of linolenoyl ethanolamine |
| CN103301136B (en) * | 2013-05-21 | 2015-04-15 | 成都旗美生物科技有限公司 | Combined medical and health-care medicine of naringenin |
| CN103877100B (en) * | 2013-05-21 | 2016-08-10 | 成都旗美健康食品有限公司 | Medical and for health care medicine of the associating of linolenic acid acyl ethanol amine |
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| Publication number | Publication date |
|---|---|
| CN1278689C (en) | 2006-10-11 |
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