Pepper C, Hooper K, Thomas A, Hoy T, Bentley P
Department of Haematology, Llandough Hospital, Penlan Road, Penarth, South Glamorgan, UK, CF64 2XX.
Leuk Lymphoma. 2001 Jul;42(3):491-8. doi: 10.3109/10428190109064606.
We have previously shown that the Bcl-2 antisense oligonucleotide ODN 2009 can induce apoptosis in B-cell chronic lymphocytic leukaemia (B-CLL) cells. In this study we evaluated whether ODN 2009 could increase the sensitivity of B-CLL cells to Chlorambucil-induced cell death in vitro in order to establish whether the notion of antisense-mediated chemosensitisation could be applied to B-CLL. Bcl-2 antisense in combination with Chlorambucil resulted in a more marked reduction in Bcl-2 protein expression (p = 0.003), enhanced Bax expression (p < 0.0001) and increased apoptosis when compared to cells incubated with Chlorambucil alone (p = 0.03). This increased in vitro cytotoxicity demonstrates a proof of the concept that a combination of Bcl-2 antisense oligonucleotides with conventional chemotherapeutic drugs may elicit an enhanced therapeutic effect in B-CLL and should therefore be considered for further investigation in the form of a clinical trial.
我们之前已经表明，Bcl-2反义寡核苷酸ODN 2009可诱导B细胞慢性淋巴细胞白血病（B-CLL）细胞凋亡。在本研究中，我们评估了ODN 2009是否能在体外增加B-CLL细胞对苯丁酸氮芥诱导的细胞死亡的敏感性，以确定反义介导的化学增敏概念是否可应用于B-CLL。与单独用苯丁酸氮芥孵育的细胞相比，Bcl-2反义寡核苷酸与苯丁酸氮芥联合使用导致Bcl-2蛋白表达更显著降低（p = 0.003），Bax表达增强（p < 0.0001），凋亡增加（p = 0.03）。这种体外细胞毒性的增加证明了这样一个概念，即Bcl-2反义寡核苷酸与传统化疗药物联合使用可能在B-CLL中产生增强的治疗效果，因此应以临床试验的形式考虑进一步研究。
