The role of Eag and HERG channels in cell proliferation and apoptotic cell death in SK-OV-3 ovarian cancer cell line
The role of Eag and HERG channels in cell proliferation and apoptotic cell death in SK-OV-3 ovarian cancer cell line
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DOI：
10.1186/1475-2867-11-6
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发表时间：
2011-03-10
影响因子：
5.8
通讯作者：
Khan, Raheela
中科院分区：
文献类型：
--
作者：
Asher, Viren;Warren, Averil;Khan, Raheela
背景资料：电压门控钾（K+）通道Eag和HERG通过与细胞周期变化和程序性细胞死亡相关而与各种癌症的发病机制有关。这些通道在卵巢癌发病和进展中的作用尚不清楚。Eag和HERG通道影响卵巢癌细胞增殖的机制的理解是必需的，因此，我们研究了它们在细胞增殖中的作用和它们对卵巢癌细胞的细胞周期和凋亡的影响。方法：使用免疫荧光和蛋白质印迹法在SK-OV-3细胞中测定Eag和HERG的存在。用MTS法检测Eag通道阻断剂（丙咪嗪和氯非铵）和HERG通道阻断剂（E-4031和ergtoxin）对细胞增殖的影响，并进一步用流式细胞术检测它们对细胞周期和凋亡的影响。丙咪嗪（P < 0.001）和ergtoxin（P < 0.05）对SK-OV-3细胞的增殖有明显的抑制作用。与ergtoxin孵育的细胞导致细胞在S期和G2/M期的积累，而与E-4031孵育后细胞在S期积累，对凋亡没有影响。结论：Eag和HERG通道在卵巢癌细胞株SK-OV-3中均有表达，并在细胞增殖中发挥作用。HERG通道影响细胞周期，而Eag通道参与卵巢癌细胞凋亡的抑制。Eag通道家族可能成为卵巢癌治疗的新靶点。
Background: The voltage gated potassium (K+) channels Eag and HERG have been implicated in the pathogenesis of various cancers, through association with cell cycle changes and programmed cell death. The role of these channels in the onset and progression of ovarian cancer is unknown. An understanding of mechanism by which Eag and HERG channels affect cell proliferation in ovarian cancer cells is required and therefore we investigated their role in cell proliferation and their effect on the cell cycle and apoptosis of ovarian cancer cells.Methods: The presence of Eag and HERG was determined in SK-OV-3 cells using immunofluorescence and western blotting. The effect of the Eag blockers (imipramine and clofilium) and HERG blockers (E-4031 and ergtoxin) on cell proliferation was assessed using the MTS assay with further investigation of their role in the cell cycle and apoptosis determined by flow cytometry.Results: Eag and HERG channels were present in the cytoplasm and nuclei of SK-OV-3 cells. There was significant inhibition of proliferation of SK-OV-3 cells by imipramine (P < 0.001) and ergtoxin (P < 0.05) at 72 hours of culture. Incubation of cells with ergtoxin led to the accumulation of cells in the S and G2/M phase, while cells accumulated in S phase after incubation with E-4031, with no effect on apoptosis. Imipramine did not affect the cell cycle but increased the proportion of SK-OV-3 cells undergoing early apoptosis.Conclusion: Both Eag and HERG channels are expressed in SK-OV-3 ovarian cancer cells and have a role in cell proliferation. HERG channels affect the cell cycle while Eag channels are implicated in the inhibition of apoptosis of ovarian cancer cells. The family of Eag channels may represent a new therapeutic target for the treatment of ovarian cancer.