Voltage-gated K+ channels are associated with cell proliferation and cell cycle of ovarian cancer cell.
OBJECTIVE
To study the role of Voltage-gated potassium ion channels (Kv) in cell proliferation and cell cycle of ovarian cancer cell.


METHODS
The effects of voltage-gate K+ channels on human ovarian cancer cell line (A2780 cell) proliferation and cell cycle were observed by means of MTT and flow cytometry. A variety of K+ channel blockers were used in order to differentiate the critical subtype of K+ channels involved. Mechanism of K+ channel in cell proliferation was explored by studying the relationship between the K+ channel and Ca2+ entry. Kv and L-type Ca2+ channel gene expressions were determined by RT-PCR.


RESULTS
4-Aminopyridine, an inhibitor of voltage-gated K+ channels, significantly inhibited the proliferation of A2780 cells as measured by MTT. 4-Aminopyridine also significantly affected the cell cycle, which increased the percentage of cells in G0/G1, and reduced the percentage of cells in S phase and G2/M phase. Non-selective K+ channel blockers tetrapentylammonium (TPeA) and verapamil had similar inhibitory effects on A2780 cell proliferation and cell cycle. In contrast, iberiotoxin, a selective inhibitor of KCa channels, and glibenclamide, a potent inhibitor of KATP channels, had no effect on the cell proliferation and cell cycle of A2780. Moreover K+ channels inhibitor, TPeA and verapamil, can blocked Ca2+ influx in these cells.


CONCLUSIONS
Voltage-gated K+ channels play an important role in the proliferation and cell cycle of ovarian cancer cell. It is likely that the influence of Kv channels on A2780 cell proliferation and cell cycle is mediated by a Ca2+-dependent mechanism.
Zhanping
Weng
W
Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, Shandong, PR China.
Xiaoyu
Pan
P
Na
Cui
C
Shenglan
Wang
W
Bo
Wang
W
D015761:4-Aminopyridine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014700:Verapamil / Q000494:pharmacology
D024642:Potassium Channels, Voltage-Gated; D000644:Quaternary Ammonium Compounds; C027435:tetrapentylammonium; D015761:4-Aminopyridine; D014700:Verapamil; D002118:Calcium