PI3K/Akt is involved in bufalin-induced apoptosis in gastric cancer cells
PI3K/Akt is involved in bufalin-induced apoptosis in gastric cancer cells
复制标题
PI3K/Akt 参与蟾蜍灵诱导的胃癌细胞凋亡
DOI：
10.1097/cad.0b013e3283160fd6
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发表时间：
2009-01-01
影响因子：
2.3
通讯作者：
Liu, Yunpeng
中科院分区：
文献类型：
--
作者：
Li, Dan;Qu, Xiujuan;Liu, Yunpeng
蟾毒灵是中药禅素的有效成分，有报道称蟾毒灵能诱导一些人白血病和实体癌细胞的凋亡。然而，蟾毒灵诱导细胞凋亡的确切机制尚不清楚。在本研究中，我们证明蟾毒灵对胃癌MGC803细胞的增殖具有剂量依赖性和时间依赖性。在低浓度（20 nmol/l）下，蟾毒灵诱导m期细胞周期阻滞，而在高浓度（80 nmol/l）下，蟾毒灵诱导MGC803细胞凋亡。蟾毒灵在MGC803细胞凋亡过程中增加了Bax/Bcl-2比值，激活了caspase-3。需要注意的是，蟾毒灵短暂激活了磷脂酰肌醇3-激酶(PI3K)/Akt信号通路，然后完全抑制了它，上调了Casitas b谱系淋巴瘤（Cbl）家族的泛素连接酶，PI3K的上游调节剂。蟾毒灵与pi3k特异性抑制剂LY294002联合使用可促进细胞凋亡，但细胞外调节蛋白激酶特异性抑制剂PD98059对蟾毒灵诱导的细胞凋亡无显著影响。这些结果提示PI3K/Akt通路可能在蟾毒灵诱导的胃癌MGC803细胞凋亡中起关键作用。
Bufalin is the active ingredient of the Chinese medicine Chan Su, and it has been reported that bufalin induces apoptosis in some human leukemia and solid cancer cell lines. The exact mechanism of bufalin-induced apoptosis is, however, still not clear. In this study, we demonstrated that bufalin inhibited the proliferation of gastric cancer MGC803 cells in a dose-dependent and time-dependent manner. At a low concentration (20 nmol/l), bufalin induced M-phase cell cycle arrest, whereas at a high concentration (80 nmol/l) it induced apoptosis in MGC803 cells. Bufalin increased the Bax/Bcl-2 ratio and activated caspase-3 during the apoptotic process of MGC803 cells. It should be noted that bufalin transiently activated the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and then inhibited it completely, and upregulated the Casitas B-lineage lymphoma (Cbl) family of ubiquitin ligases, upstream modulators of PI3K. A combination of bufalin and LY294002, a PI3K-specific inhibitor, enhanced apoptosis, but PD98059, an extracellular-regulated protein kinase-specific inhibitor, had no significant effect on bufalin-induced apoptosis. These results suggested that the PI3K/Akt pathway might play a key role in bufalin-induced apoptosis in gastric cancer MGC803 cells.