| Cutaneous T cell lymphoma mainly consists of mycosis fungoides andSezarisyndrome, which occur in the skin malignant tumor, the tumor cells withinfiltrationability, and can invade the skin, lymph nodes and internal organs, theincidence increased year by year, in non Hodgkin’s lymphoma it has risen tosecond,serious impact on human health.The granuloma fungoides (also known asmycosisfungoides, MF), only the first invade the skin, manifesting as erythema orplaques, if not treated in time, will develop to tumor stage, and ultimately affect thelives of patients. When given the strong radiation or chemotherapy in the early stage,will bring great mental stress to patients, also will bring harm to the health ofpatients.Therefore, selecting suitable drugs in different period become the researchfocus in the field of cutaneous T cell lymphoma treatment.Acitretin drugs are a group of natural vitamin A compounds with similarstructure, can adjust epithelial cells and other cell growth and differentiation,inhibitthe growth of malignant cells, and can regulate the immune and inflammatoryprocesses.Interferon is a kind of glycoprotein produced by virus, wich can inhibitvirus, anti tumor and regulate immunization.At present,the human interferon alphaof the clinical application inclue interferon(leukocyte interferon), interferon beta,(fibroblast interferon), interferon gamma(interferon). Acitretin and interferon arerespectively endogenous and exogenous inducer of differentiation, the combination ofthe two drugs can improve thesensitivity of tumors to inducer, reduce dosage, reducethe toxic side effect, so as to improve the therapeutic effect. But in cutaneous T celllymphoma research their effections are rarely reported. Objective:To discuss the effect and possible mechanism of acitretin and IFN-αin theprocess of inhibition of proliferation of human cutaneous T cell lymphoma bydetecting the proliferative inhibition and IL-15expression of human cutaneous Tcell lymphoma cell line Hut78affected by different concentration of acitretin、IFN-αand the combination of them. To provide a theoretical basis for the treatment ofcutaneous T cell lymphoma by acitretin and IFN-α.Method:1cell cultureHUT78cells were cultured in IMDM culture medium containing20%fetalbovine serum (containing penicillin100U/ml, streptomycin100U/ml,PH7.2), at37℃、saturated humidity,、5%CO2in incubator.2CCK8method detect the effects of acitretin and IFN-αon proliferativeinhibition of human Hut78cell.2.1The effects of different concentrations of acitretin（0.1umol／L﹑1.0umol／L﹑10umol／L） on the proliferation of human Hut78cell after24h、48h、72hrespectively.2.2The effects of different concentrations of IFN-α(5000IU/ml﹑10000IU/ml﹑20000IU/ml) on the proliferation of human Hut78cell after24h、48h、72hrespectively.2.3The effects of different concentrations of combination of IFN-αand acitretin（0.1umol／L acitretin+5000IU/ml IFNα、1.0umol／L acitretin+10000IU/ml IFNα、10umol／L acitretin+20000IU/ml IFNα）on the proliferation of human Hut78cell after24h、48h、72h respectively.3To observe differentiation and morphology of human HUT78cell after affectedby each group of drugs under inverted phase contrast microscope.4ELISA method to detect IL-15expression of human HUT78cell fter affectedby each group of drugs.5Using SPSS13.0statistical package to analyse experimental results in the wayof variance, P<0.05means statistical significance. Results1CCK8method detect the effects ofeach group of drugs on proliferativeinhibition of human Hut78cell.1.1There are significant differences in each group of acitretin （p＜0.05）.Inhibitory effect of different concentration of acitretin on proliferation ofhuman HUT78cel ls showed a significant concentration dependent and timedependent1.2There are significant differences in each group of IFN-α （p＜0.05）.Inhibitory effect of different concentration of IFN-αon proliferation of humanHUT78cells showed a significant concentration dependent and time dependent.1.3There are significant differences in each group of combination of acitretinand IFN-α（p＜0.05）.Inhibitory effect of different concentration of combination ofacitretin and IFN-αon proliferation of human HUT78cells showed a significantconcentration dependent and time dependent.The inhibitory effect of combinationgroup was enhanced, compared with the single use,and the inhibition increases withthe increasing concentration.There is a significant difference (P <0.05).2The effects of acitretin and IFN-αon differentiation and morphology of humanHUT78cell.The negative control group cells were round or oval, suspendedgrowth,distribution, some clustered into groups with the same size, shape, strongproliferation, occasional nuclear pyknosis;After24hours of effect of acitretin onHUT78cells, the cell growth was poorer,cell shrinked、ruptured, partial cells necrosed,formated debris of cell.With the increasing concentration of acitretin and with thetime extending, the phenomenon is more obvious;Cells affected by IFN-αwerebipolar change, HUT78cells became more narrow, the numberof rupture cellincreased,With the increasing concentration of IFN-α and with the time extending,the phenomenon is more obvious;The combination groups cells grew more slowly, thecell number was significantly reduced, the cell debris increased.3ELISA method to detect IL-15expression of human HUT78cell fter affected by each group of drugs.Compared with the negative control group, the treatmentgroup decreased the IL-15expression of HUT78cell, and with the increasingconcentration of drug and time extending, decrease was more obvious.Comparisonbetween group differences was significant (P <0.05).Conclusion:1Acitretin and IFN-α can inhibit the proliferation of HUT78cells, and withthe increasing concentration and time, effecton inhibition of HUT78cellproliferation rate showed a dose dependent and time correlation.2The rate of proliferative inhibition of HUT78cell induced by acitretin andIFN-α is better than the single application of acitretin or IFN-α, the combinationof the two drugs had synergistic effect.3The inhibition effect of acitretin and IFN-α on HUT78cells may be related todown regulate the expression of IL-15, this may be related to the mechanism ofproliferative inhibition of tumor. |
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