1-ALPHA,25-DIHYDROXYVITAMIN D-3 INHIBITS THE INVASIVE POTENTIAL OF HUMAN BREAST-CANCER CELLS IN-VITRO

Using the Boyden chamber invasion assay, the effect of 1 alpha,25-dihy droxyvitamin D-3 [1 alpha,25(OH)(2)D-3] on the invasiveness of the hig hly invasive, oestrogen receptor-negative human breast cancer cell lin e MDA-MB-231 was examined. The MDA-MB-231 cells were shown to contain high-affinity receptors for 1 alpha,25(OH)(2)D-3 with a K-d of 1.5 X 1 0(-11) M. When the cells were treated with 1 alpha,25(OH)(2)D-3 for 4 days before the assay was performed, a dose-dependent inhibition of th eir invasive potential was demonstrated. Fifty per cent inhibition of invasion was obtained with a concentration of 13 pM of 1 alpha,25(OH)( 2)D-3. However, when the cells were treated for only 6 h during the as say, no inhibitory effect was seen. The process of migration was also affected by treatment with 1 alpha,25(OH)(2)D-3 for 4 days, although t he inhibition was not of the same magnitude as seen for the invasion. Fifty per cent inhibition of migration occurred at a concentration of 3.2 nM of 1 alpha,25(OH)(2)D-3 (250 times higher than in the invasion assay). Inhibition of invasion and migration was not due to the known anti-proliferative effect of 1 alpha,25(OH)(2)D-3, as no growth reduct ion could be demonstrated with treatment up to 5 days. Based on the pr esent investigation it can therefore be concluded that 1 alpha,25(OH)( 2)D-3 is able to inhibit tumour cell invasiveness by a mechanism which is not exclusively based on its anti-proliferative and anti-migrative effects.