FAS,FASL及Bcl-2在化疗药物诱导RMA细胞凋亡过程中的表达

本研究通过测定RMA细胞Fas,FasL和Bcl-2表达的变化，探讨其在细胞凋亡过程中的作用。在培养的小鼠T淋巴瘤RMA细胞系中加化疗药物地塞米松（DEX）、足叶乙甙（VP－16）、三氧化二砷（As2O3)及维甲酸（ATRA）以及培养细胞中先分别与细胞国子IL－2，IL－6或GM－CSF共同培养后再加入上述药物，观察对细胞凋亡的影响及细胞凋亡过程中Fas,FasL mRNA,Fas及Bcl-2抗原的表达。DEX和VP－16能上调Fas和FasL表达，促进细胞凋亡，Bcl-2表达无变化。ATRA可下调Bcl-2表达，但不影响Fas和FasL系统，也未观察到有细胞凋亡。As2O3可以诱导细胞凋亡,但Fas,FasL及Bcl-2表达均无变化。提示不同药物对一种细胞可能通过不同的信号途径诱导调亡，而Fas系统诱导的细胞凋亡需要Fas和FasL共同参与。单独用IL－2，IL－6或GM－CSF虽然使Fas蛋白增加，但不引起细胞凋亡；如同时并用IL－2和IL－6则Fas和FasL表达均上升，并诱导细胞凋亡。上述细胞因子与化疗药物并用时可减低药物量，促进药物的凋亡诱导作用。在无FasL表达情况下，抗Fas单克隆抗体能诱导RMA细胞凋亡。实验结果表明，细胞因子与化疗药物可协同作用诱导细胞凋亡，Fas-FasL系统参与DEX和VP－16诱导的RMA细胞凋亡过程，不同的药物可以通过不同的信号途径诱导细胞凋亡。

The Expression of Fas, FasL and Bcl-2 on RMA Cells during the Process of Apoptosis Induced by Chemotherapeutic Drugs

The objective of the study is to explore the effect of Fas, FasL and Bcl 2 on the process of apoptosis induced by chemotherapeutic drugs through detecting the expression of Fas, FasL and Bcl 2 on murine lymphoma cell line RMA. Dexamethasone(DEX), etoposide(VP 16), arsenic trioxide(As 2O 3) and all trans retinoic acid(ATRA) were added to the RMA cells as well as to the cells preincubated with interleukin 2(IL 2), interleukin 6(IL 6) or granulocyte macrophage colony stimulating factor(GM CSF), respectively. The effect on apoptosis was observed and the expression of Fas and FasL mRNA as well as the expression of Fas and Bcl 2 antigen were measured. DEX and VP 16 could promote apoptosis of RMA cells while upregulating the expression of Fas and FasL without affecting the exppression of Bcl 2. ATRA downregulated the expression of Bcl 2 without any change of Fas and FasL, and no apoptosis of RMA cells induced by ATRA was observed. Although As 2O 3 induced apoptosis of RMA cells, it did not affect the expression of Fas, FasL and Bcl 2, which suggested that different drugs induce apoptosis of the same kind of cells by different signal transduction system and apoptosis induced by Fas system needed the coexistence of Fas and FasL. Although IL 2, IL 6 and GM CSF upregulated the expression of Fas protein when adding to RMA cells separately, none of them induced apoptosis. Apoptosis could be induced by combination of IL 2 and IL 6 along with the upregulation of Fas and FasL. The cytokines facilitated the apoptotic action of chemotherapeutic drugs, the drug concentration for inducing apoptosis decreased and the time period of starting apoptosis shortened. Apoptosis could be observed without the expression of FasL when anti Fas antibody was added to RMA cells. The results demonstrated that there was synergistic effect of chemotherapeutic drugs and some cytokines for induction of apoptosis. Fas FasL system participated in the apoptosis induced by DEX and VP 16; different drugs induce apoptosis by different pathway of signal transduction.