[Influence of 4-aminopyridine on cell proliferation through inhibiting voltage-gated K+ channel in ovarian cancer]

Abstract

Objective: To study the inhibition of cell proliferation by 4-aminopyridine (4-AP) in the human ovarian cancer cell SKOV3.

Methods: The expression of voltage-gated K(+) channel on the SKOV3 cell line was detected by reverse transcription polymerase chain reaction. Inhibition of voltage-gated K(+) current by 4-AP through the whole-cell patch-clamp technique on SKOV3 cell line was recorded. The influence on the cell-cycle of the SKOV3 cell line by 4-AP was observed by flow cytometry and the inhibition of the cell proliferation was studied using methyl thiazolyl tetrazolium (MTT) method.

Results: Voltage-gated K(+) channel was expressed in SKOV3 cell. Exposure of the SKOV3 cell to 5 mmol/L 4-AP reduced K(+) current by 52.5%. The 4-AP at 5 mmol/L significantly effected the progression of cell cycle with a 72 h treatment of SKOV3 cell. Exponentially growing cells without inhibitors had a distribution of 39.7% in G(0)/G(1) phase, 57.3% in S phase, and 3.0% in G(2)/M phase. In 4-AP-treated cells, the proportion of G(0)/G(1) cells increased significantly to 62.3% (P < 0.05), while there was a significant decrease in S phase cells (36.2%, P < 0.05) and G(2)/M phase (1.4%, P < 0.05). Incubation of the SKOV3 cells with 0.1, 1, 5, 10, 15, 20 mmol/L 4-AP resulted in a concentration-dependent reduction in the number of viable cells as compared with the control, and the inhibition rate was 17.5%, 35.0%, 54.6%, 69.1%, 71.2%, 72.8% respectively (vs control, P < 0.01).

Conclusion: The voltage-gated K(+) channels expressed by SKOV3 play an important role in SKOV3 cell proliferation.