A novel combination: ranpirnase and rosiglitazone induce a synergistic apoptotic effect by down-regulating Fra-1 and Survivin in cancer cells.
A novel combination: ranpirnase and rosiglitazone induce a synergistic apoptotic effect by down-regulating Fra-1 and Survivin in cancer cells.
复制标题
一种新颖的组合：兰匹那酶和罗格列酮通过下调癌细胞中的 Fra-1 和 Survivin 诱导协同凋亡效应。
DOI：
10.1158/1535-7163.mct-08-0308
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发表时间：
2008
影响因子：
5.7
通讯作者：
Littenberg,Benjamin
中科院分区：
文献类型：
--
作者：
Ramos-Nino,MariaE;Littenberg,Benjamin
Accumulating evidence supports the idea that two known phosphatidylinositol 3′-kinase (PI3K) downstream proteins, Fra-1 and Survivin, are potential targets for cancer therapy. Increased expression of Fra-1, a Fos family member of the transcription factor activator protein-1, has been implicated in both the maintenance and the progression of the transformed state of several cancer cells. In addition, high Survivin expression in tumors correlates with more aggressive behavior, lower response to chemotherapeutic drugs, and shortened survival time. Previously, we reported that, in malignant mesothelioma cells with increased PI3K activity, small-molecule inhibitors of the PI3K/AKT pathway acted cooperatively with the amphibian RNase chemotherapeutic drug ranpirnase to inhibit cell growth. Because the thiazolidinedione antidiabetic drug rosiglitazone targets the PI3K/AKT pathway, we investigated the effect of the combination of these two drugs in cell survival in several cancer cell lines. We show here that the combination of ranpirnase and rosiglitazone synergistically decreases cell viability and increases cell apoptosis in several cancer cell lines. Cell killing is associated with decreased Fra-1 and Survivin expression and knockdown ofFra-1increases cell killing by ranpirnase in a dose-dependent manner but not by rosiglitazone. The drug combination does not have a synergistic effect on killing inFra-1knockdown cells, showing thatFra-1modulation accounts in part for the synergism. The novel drug combination of ranpirnase and rosiglitazone is a promising combination to treat cancers with increased PI3K-dependent Fra-1 expression or Survivin. [Mol Cancer Ther 2008;7(7):1871–9]
