摘要
目的探讨组蛋白去乙酰化酶抑制剂曲古抑菌素 A(trichostatin A,TSA)对 B 细胞淋巴瘤的体外作用机制,为临床应用提供理论依据。方法选择对多柔比星耐药的 B 淋巴瘤细胞系 SU-DHL-4为研究对象,MTT 法检测 TSA 对其生长抑制作用,RT-PCR 检测 TSA 对转录因子 PRDM1和 c-myc 的影响。结果纳摩尔浓度的 TSA 体外作用48h 即能够显著抑制 SU-DHL-4细胞系的体外增生,且呈剂量依赖性;SU-DHL-4细胞系中表达转录因子PRDM1α和β两种转录本,且比例异常,高表达与肿瘤发生相关的 PRDM1β转录以及其下游基因c-myc;150 nmol/L TSA 作用细胞12h 能够显著增加结构功能正常的 PRDM1α表达,抑制 PRDM1β表达,24h 后 c-myc 表达受抑制。结论 TSA 可以显著抑制耐药B淋巴瘤细胞系 SU-DHL-4的增生,纠正转录因子PRDM1α和β表达比例,继而抑制下游靶基因c-myc 表达是其抗增生作用的机制之一。
Objective To explore the effect of trichostatin A(TSA),a histone deaeetylase inhibitor (HDACI),on B cell lymphoma in vitro and provide evidence for its usage in clinic.Methods SU-DHL-4 cell line was applied for the study,which is resistant to doxorubicin.We detected the growth arrest of SU- DHL-4 treated by TSA with MTT assay and evaluate the alteration of PRDM1 and c-myc with RT-PCR.Re- stilts TSA(nmol/L)dose-dependently suppressed the proliferation of SU-DHL-4 after 48 hours of treatment; SU-DHL-4 expressed two transcripts of PRDMI gene,i.e.,α and β,and its target gene c-myc.Moreover,the level of PRDMI1β trancript was higher than PRDM1α,which is responsible for oncogenesis;150 nmol/L TSA increased PRDM1α and suppressed PRDM1β expression after 12 hours and decreased c-myc expression after 24 hours administration.Conclusion TSA can induce growth arrest of SU-DHL-4 cell line by alteration of PRDM1α and suppressing PRDM1β and following the downregulation of c-myc.
出处
《白血病．淋巴瘤》
CAS
2007年第6期416-418,共3页
Journal of Leukemia & Lymphoma
