Department of Surgery, University of California, San Francisco, CA 94115, USA.
Oncol Rep. 2010 Dec;24(6):1677-81. doi: 10.3892/or_00001033.
Phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway plays pivotal roles in fundamental cellular functions including cell proliferation and cell survival. Its deregulation has been implicated in many types of human malignancies. We investigated the role of PI3K/AKT signaling pathway in human malignant pleural mesothelioma (MM). Here, we report that aberrant activation of the PI3K/AKT signaling pathway is associated with cell cycle progression in MM cells. Inhibition of the PI3K activity by its small molecule inhibitor LY294002 led to significant G1 cell cycle arrest and suppression of cell proliferation in all MM cell lines that we examined. In addition, we found that the protein level of p27Kip1 was up-regulated and the protein level of cyclin D1 was down-regulated following LY294002 treatment in those MM cell lines. However, no noticeable apoptosis induction was observed following 24 h of LY294002 treatment in those MM cell lines. These results confirm that the PI3K/AKT signaling pathway is aberrantly active and plays a critical role for the cell cycle progression in human MM cells.
磷脂酰肌醇 3-激酶（PI3K）/AKT 信号通路在包括细胞增殖和细胞存活在内的基本细胞功能中发挥着关键作用。其失调与多种人类恶性肿瘤有关。我们研究了 PI3K/AKT 信号通路在人类恶性胸膜间皮瘤（MM）中的作用。在这里，我们报告 PI3K/AKT 信号通路的异常激活与 MM 细胞的细胞周期进展有关。我们研究的所有 MM 细胞系中，其小分子抑制剂 LY294002 抑制 PI3K 活性可导致显著的 G1 细胞周期停滞和细胞增殖抑制。此外，我们发现 LY294002 处理后，这些 MM 细胞系中的 p27Kip1 蛋白水平上调，cyclin D1 蛋白水平下调。然而，在这些 MM 细胞系中，LY294002 处理 24 小时后，未观察到明显的细胞凋亡诱导。这些结果证实 PI3K/AKT 信号通路异常活跃，在人类 MM 细胞的细胞周期进展中起着关键作用。
