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Comparison Of The Inhibitory Effects Of Five Glucocorticoids On Hematopoietic Malignant Cells In Vitro

Posted on:2013-10-04Degree:MasterType:Thesis
Country:ChinaCandidate:S S DengFull Text:PDF
GTID:2234330374952316Subject:Hematology
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【Objective】 Glucocorticoids play a pivotal role in the tumors, especially hematologicmalignancies, but the use of glucocorticoid, including the choice of the type ofglucocorticoid, the time and dose of administration vary for different malignancies, even invarious regimens for the same malignancy. There was no literature reports about the reasonof the various choice of glucocorticoid. We often exchange the glucocorticoid in a regimenfor another type based on the equivalent anti-inflammatory dose, but the equivalentanti-inflammatory dose may not be applicable in the circumstance of exerting theiranti-tumor or immunosuppressive activity. This study was designed to compare the activityof inhibition of cell proliferation and cell viability among five commonly usedglucocorticoids in several hematological malignant cell lines, and to explore whether theanti-inflammatory equi-effective dose conversion relationship also applies to theiranti-tumor effect.【Methods】 Myeloma cell lines(U266、RPMI8226、NCI-H929), leukemia cell lines(Jurkat、NB-4)and lymphoma cell line(Raji) were cultured in medium containing variousconcentrations of glucocorticoids (hydrocortisone, prednisone, prednisolone,methylprednisolone and dexamethasone) for24hours, the proliferation ability was testedby methylthiazolyl tetrazolium method (MTT) and the cell viability was tested by trypanblue counting method. By using the IC50of hydrocortisone as a standard, we compared therelative ability of anti-tumor of five glucocorticoids.【Results】 In vitro, prednisone showed low potency both in inhibiting tumor cellproliferation and viability; Nearly all kinds of steroids have no effect on the growth ofNB-4cell. The five glucocorticoids’ ability to block cell proliferation and cellular viabilityin different malignancies were showed as follows: the relative anti-proliferation potencywas methylprednisolone> prednisolone> dexamethasone> hydrocortisone, and the relativepotency ratios were7.2:6.8:4.2:1in U266,6:4:3:1in NCI-H929cells;6.8:7.6:3.3:1inRPMI8226cells;34:17:7.6:1in Raji cells;5.3:3:1.4:1in Jurkat cells; the relativeinhibition in cell activity potency was methylprednisolone> prednisolone>dexamethasone> hydrocortisone,too, and the relative potency ratios were2.3:2:1.8:1inU266cells;8.8:1.6:0.8:1in NCI-H929cells;2.8:1.2:1.9:1in RPMI8226cells;17.7:3.2:1.9:1in Raji cells;4.2:1.5:1.2:1in Jurkat cells. These results does not parallel theknown relative anti-inflammatory potency ratio, which are dexamethasone>methylprednisolone> prednisolone> hydrocortisone(25:5:4:1),and they are also different from relative immunosuppressive potency ratio,which are methylprednisolone>hydrocortisone>dexamethasone> prednisolone(9:1:0.8:0.3).【Conclusions】Equi-effective anti-inflammatory dose conversion relationship amongglucocorticoids does not parallel their anti-tumor activity in hematological malignancies,but our results awaits further investigations to be confirmed.
Keywords/Search Tags:glucocorticoids, hematological malignant cells, cell proliferation, cellviability
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