A Src family inhibitor (PP1) potentiates tumor-suppressive effect of connexin 32 gene in renal cancer cells
A Src family inhibitor (PP1) potentiates tumor-suppressive effect of connexin 32 gene in renal cancer cells
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DOI：
10.1016/j.lfs.2004.10.049
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发表时间：
2005-04-22
期刊：
影响因子：
6.1
通讯作者：
Yano, T
中科院分区：
文献类型：
--
作者：
Fujimoto, E;Sato, H;Yano, T
连接蛋白（Cx）基因对肿瘤细胞产生负面生长影响，具有一定的细胞特异性。我们最近报道，Cx32 由于抑制 Src 依赖性信号传导而在肾癌细胞中充当肿瘤抑制基因。与之前的研究一致，我们在这里检查了 Src 家族抑制剂 (PP1) 是否可以增强 Cx32 在人肾细胞癌 Caki-2 细胞中的肿瘤抑制作用。为了阐明 PP1 的潜力，我们使用 Cx32 转染的 Caki-2 细胞和模拟转染的 Caki-2 细胞，评估了 PP1 在体外和体内对两个细胞克隆的细胞毒性作用的差异。 PP1在较低剂量下对Cx32阳性表达的Caki-2细胞表现出比Cx32阴性表达更强的细胞毒作用。在裸鼠异种移植模型中也观察到了这种潜力。其作用的发挥主要取决于细胞凋亡的诱导，而不是对细胞生长的控制。与此事件相关的是，Caki-2 细胞中 Cx32 表达和 PP1 处理相结合引起了抗凋亡分子（Bcl-2 和 Bcl-xL）的减少。这些结果表明PP1通过减少抗凋亡分子来增强肾癌细胞中连接蛋白32基因的肿瘤抑制作用。 (c) 2005 Elsevier Inc. 保留所有权利。
Connexin (Cx) genes exert negative growth effects on tumor cells with certain cell specificity. We have recently reported that Cx32 acts as a tumor suppressor gene in renal cancer cells due to the inhibition of Src-dependent signaling. In line with the previous study, here we examined if a Src family inhibitor (PP1) could potentiate tumor-suppressive effect of Cx32 in Caki-2 cell from human renal cell carcinoma. In order to clarify the potentialization of PP1, using Cx32-transfected Caki-2 cells and mock-transfected Caki-2 cells, we estimated difference in cytotoxic effect of PP1 on the two cell clones in vitro as well as in vivo. PP1 showed more cytotoxic effect on Caki-2 cells having Cx32 positive expression than that of Cx32 negative expression at lower doses. This potentialization was also observed in xenograft model of nude mice. The potentialization of the effect mainly depended on the induction of apoptosis but not the control of cell growth. In conjugation with this event, the reduction of anti-apoptotic molecules (Bcl-2 and Bcl-xL) was caused by the combination of Cx32 expression and PP1 treatment in Caki-2 cells. These results suggest that PP1 potentiates tumor-suppressive effect of connexin 32 gene in renal cancer cells through the reduction of anti-apoptotic molecules. (c) 2005 Elsevier Inc. All rights reserved.