The Proliferation Effects Of The Intermediate Conductance Calcium-activated K~+Channel Inhibitors On The Breast Cancer Cell MDA-MB-231

[Object] To explore the proliferation effects of the intermediate conductance calcium-activated K+channel (IK1) inhibitors on the triple negative breast cancer cell MDA-MB-231.[Experimental approach] MDA-MB-231cells were cultured in vitro. The function and protein expression of IK1in MDA-MB-231cells was examined using western blot analysis, immunofluorescence technique and patch clamp technique (whole-cell electrophysiological recordings). The effect of the inhibitors of IK1(Clotrimazole and TRAM-34) on the cell growth and proliferation of MDA-MB-231cells were carried out using MTT proliferation assay, colony formation assay and flow cytometry. All data were analyzed by the statistics software of SPSS19.0and some other related softwares.[Results] Functional IK1was expressed in MDA-MB-231cells, mainly distributing on the cell membrane. The IK1specific inhibitors, clotrimazole and TRAM-34, reduced the cell proliferation in a dose-dependent manner (10-40μM), with the maximum inhibition rate50±7.0%(P<0.05) and20±4.0%(P<0.05) respectively. Compared with the control group, in the treatment group, the normal cell proportion decreased significantly, the proportion of the early apoptosis cells increased apparently (P<0.05), but the percentage of the middle and late apoptosis cells and necrosis cells mainly the same. With the concentration (10μM and20μM) or/and delivery during (24h-72h) increasing, the proportion of the early apoptosis cells increased (P<0.05).[Conclusion] Our findings indicate that MDA-MB-231can be used as a kind of cell model to study IK. Clotrimazole and TRAM-34exhibit inhibitory effect on MDA-MB-231cell proliferation depending on concentrations. TRAM-34may induce the apoptosis of MDA-MB-231in a dose and time-dependent manner.