N1-鸟嘌呤基-1,7-二氨基庚烷 (GC7) 通过抑制真核翻译起始因子 5A2 (eIF5A2) 的激活和阻止肝癌细胞的上皮-间充质转化来增强阿霉素的治疗效果。
N1-guanyl-1,7-diaminoheptane (GC7) enhances the therapeutic efficacy of doxorubicin by inhibiting activation of eukaryotic translation initiation factor 5A2 (eIF5A2) and preventing the epithelial-mesenchymal transition in hepatocellular carcinoma cells.
机构信息
Department of Laboratory Medicine, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
出版信息
Exp Cell Res. 2013 Oct 15;319(17):2708-17. doi: 10.1016/j.yexcr.2013.08.010. Epub 2013 Aug 16.
Hepatocellular carcinoma (HCC) cells undergo the epithelial-mesenchymal transition (EMT) during chemotherapy, which reduces the efficacy of doxorubicin-based chemotherapy. We investigated N1-guanyl-1,7-diaminoheptane (GC7) which inhibits eukaryotic translation initiation factor 5A2 (eIF5A2) activation; eIF5A2 is associated with chemoresistance. GC7 enhanced doxorubicin cytotoxicity in epithelial HCC cells (Huh7, Hep3B and HepG2) but had little effect in mesenchymal HCC cells (SNU387, SNU449). GC7 suppressed the doxorubicin-induced EMT in epithelial HCC cells; knockdown of eIF5A2 inhibited the doxorubicin-induced EMT and enhanced doxorubicin cytotoxicity. GC7 combination therapy may enhance the therapeutic efficacy of doxorubicin in HCC by inhibiting eIF5A2 activation and preventing the EMT.
肝细胞癌 (HCC) 细胞在化疗过程中会经历上皮-间充质转化 (EMT)，这会降低基于多柔比星的化疗的疗效。我们研究了 N1-胍基-1,7-二氨基庚烷 (GC7)，它可以抑制真核翻译起始因子 5A2 (eIF5A2) 的激活；eIF5A2 与化疗耐药性有关。GC7 增强了上皮性 HCC 细胞 (Huh7、Hep3B 和 HepG2) 中多柔比星的细胞毒性，但对间充质性 HCC 细胞 (SNU387、SNU449) 影响较小。GC7 抑制了上皮性 HCC 细胞中多柔比星诱导的 EMT；eIF5A2 的敲低抑制了多柔比星诱导的 EMT 并增强了多柔比星的细胞毒性。GC7 联合治疗可能通过抑制 eIF5A2 的激活和防止 EMT 来增强多柔比星在 HCC 中的治疗效果。
Zotero 插件