Figure 4

Role of omeprazole and the AHR in downregulation of CXCR4 and inhibition of invasion in MCF-7 and MDA-MB-468 cells. (a) CYP1A1 and CXCR4 mRNA. Cells were treated with 100 or 200 μM omeprazole for 24 hr, and CXCR4 and CYP1A1 mRNA levels were determined as outlined in the Methods. (b) and (c) Role of the AHR. Cells were transfected with siAHR and treated with 200 μM omeprazole, and expression of AHR and CYP1A1 (b) and CXCR4 (c) mRNA levels were determined as outlined in the Methods. MCF-7 cells were also cotreated with 100 nM PMA. (d) Effects of omeprazole on invasion of MCF-7 cells. Cells were transfected with siCtl (non-specific) or siAHR and treated with DMSO or 200 μM omeprazole plus PMA (MCF-7 cells), and cell invasion was determined in a Boyden chamber assay as outlined in the Methods. Results (a-d) are means ± SE for at least 3 replicate determinations for each data point. Significantly (p < 0.05) increased CYP1A1 or decreased CXCR4 (*) and reversal of these effects by siAHR (**) are indicated. AHR mRNA was significantly (p < 0.05) decreased by siAHR in all 3 cell lines.