Increased chemotherapeutic activity of camptothecin in cancer cells by siRNA-Induced silencing of WRN helicase
Increased chemotherapeutic activity of camptothecin in cancer cells by siRNA-Induced silencing of WRN helicase
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DOI：
10.1248/bpb.30.1958
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发表时间：
2007-10-01
影响因子：
2
通讯作者：
Furuichi, Yasuhiro
中科院分区：
文献类型：
--
作者：
Futami, Kazunobu;Takagi, Motoki;Furuichi, Yasuhiro
Werner综合征解旋酶（WRN）参与DNA复制、双链DNA断裂修复、端粒和逆转录病毒长末端重复序列的维持等多种DNA活动。WRN基因的突变导致沃纳综合征（WS），一种常染色体隐性遗传性早衰症，与衰老相关的各种症状有关。在这项研究中，我们研究了特异性下调WRN表达的siRNA。WRN沉默显著增加喜树碱（CPT）对癌细胞的化疗活性，在疗效程度和降低有效药物剂量方面，伴随着抑制CPT引起的DNA损伤的恢复。在这里，我们提出了一种潜在的WRN-siRNA和CPT的联合治疗，期待着最大限度地减少与癌症化疗相关的不可避免的不良反应。
Werner syndrome helicase (WRN) participates in a wide range of DNA activities, including replication, double-strand DNA break repair, telomere and retrovirus long terminal repeat maintenance. Mutations of the WRN gene cause Werner syndrome (WS), an autosomal recessive premature ageing disorder associated with various symptoms related to ageing. In this study, we investigated the siRNA that specifically down-regulates WRN expression. WRN silencing increased markedly the chemotherapeutic activity of camptothecin (CPT) on cancer cells in terms of the extent of efficacy and lowering effective drug dosage, accompanied by suppressing recovery from DNA damage caused by CPT. Here, we propose a potential combination therapy of WRN-siRNA and CPT, looking forward to minimizing the inevitable adverse effects associated with cancer chemotherapy.