Effect of calcium signal on expression of HIF-1α in breast cancer cell line and invasion and metastasis of cells
AIM: To investigate the impact of the calcium signal on the expression of hypoxia-inducible factor-1 alpha( HIF-1α) in human breast carcinoma cell lines (MCF-7 and MDA-MB-231) cultured under hypoxia and the invasion and metastasis of the cells. METHODS: Human breast carcinoma cells MCF-7 and MDA-MB-231 were treated with 150 μmol/L CoCl2 to simulate the hypoxia. The cells were divided into 3 groups: control, CoCl2, and CoCl2 + verapamil (VPL) groups. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect the expression of HIF-1α mRNA in the cells. The protein expression level of HIF-1α was measured by Western Blot and immunocytochemistry. The invasion and metastasis abilities of the cells in vitro were explored by millicell chamber. RESULTS: There were expressions of HIF-1α in human breast carcinoma cells MCF-7 and MDA-MB-231. The mRNA and protein expression levels of HIF-1α under hypoxia induced by CaCl2 were higher than that of control cells ( P < 0. 01). The expression levels of mRNA and protein of HIF-1α were suppressed significantly after treatment with VPL ( P < 0. 01 ), with significant difference between MCF-7 cells and MDA-MB-231 cells (P <0. 01). The invasive and metastatic potentials of human breast cancer cells MCF-7 and MDA-MB-231 were suppressed more significantly after treatment with VPL + CoCl2 than with CoCl2 (P < 0.01) , and the suppressing effects were more significant for MDA-MB-231 than for MCF-7. CONCLUSION: Blocking the calcium signal pathway may induce the down-regulation of HIF-1α expression in breast cancer cells, so as to inhibit the invasion and metastasis potential of the cells.
calcium signalHIF-1αbreast neoplasmscell linetumorinvasion and metastasis