化疗药物与细胞因子协同作用引起小鼠T淋巴瘤细胞凋亡

Synergistic Induction of Apoptosis by Chemotherapeutic Drugs and Cytokines in Mouse T-Lymphoma Cell Line

本实验旨在了解化疗药物和细胞因子协同作用对细胞凋亡的影响。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 (VP16 )、三氧化二砷 (As2 O3 )及维甲酸(ATRA)以及培养细胞中先分别与细胞因子IL 2 ,IL 6和GM CSF共同培养后再加入上述药物 ,观察对引起细胞凋亡的影响。四种化疗药均能抑制RMA细胞增殖 ,DEX ,VP16和As2 O3 可以诱导细胞凋亡 ,单独使用ATRA不能引起RMA细胞凋亡 ,但与DEX联用时可降低DEX诱导凋亡的浓度。单用IL 2 ,IL 6或GM CSF不引起肯定的细胞凋亡 ;如同时并用IL 2和IL 6则出现肯定的细胞凋亡。化疗药物与细胞因子并用时可减低药物引发细胞凋亡的浓度 ,并使细胞凋亡发生的时间提前。实验结果表明 ,化疗药物与细胞因子在诱导细胞凋亡中具有协同作用 ,为细胞因子特别是IL 2与化疗药物配伍使用治疗恶性淋巴瘤提供了一定实验依据。

The objective of the study is to find out the synergistic effect on apoptosis resulting from the combination of chemotherapeutic drugs and some cytokines. Dexamethasone(DEX), etoposide(VP16), arsenic trioxide(As 2O 3 ) and alltrans-retinoic acid (ATRA) were added to the murine T lymphoma cell line RMA as well as to the cells preincubated with IL-2, IL-6 or GM-CSF, respectively. The effect on apoptosis was observed. All four chemotherapeutic drugs inhibited the cell proliferation. DEX,VP16 or As 2O 3,except ATRA, singly induced apoptosis of RMA cells. The DEX concentration of inducing apoptosis was reduced when it was added together with ATRA. IL-2,IL-6 and GM-CSF did not induce apoptosis when the cytokines were added to RMA separately, however, apoptosis could be induced by combination of IL-2 and IL-6. The cytokines facilitated the apoptotic action of chemotherapeutic drugs, the drug concentration for inducing apoptosis decreased and the time period of starting apoptosis shortened. The results demonstrated that there was synergistic effect of chemotherapeutic drugs and some cytokines for induction of apoptosis. It raised an experimental basis for combination of chemotherapeutic drugs and some cytokines, especially IL-2, in the treatment of malignant lymphoma.