Potent antitumor activity of 2-methoxyestradiol in human pancreatic cancer cell lines.

We examined the effect of 2-methoxyestradiol (2-ME) on the growth and tumorigenesis of human pancreatic cancer cells. 2-ME inhibited the growth of these cell lines (50-90%) in a dose- and time-dependent fashion, and terminal deoxynucleotidyl transferase staining showed that it induced apoptotic cell death. Flow cytometric analysis indicated that 2-ME-sensitive cells showed a prolonged S phase after 48 h of treatment. We used a mouse model for in vivo studies of lung metastasis and injected MIA PaCa-2 cells into the tail veins of nu/nu mice; lung colonies were formed. Mice given oral 2-ME showed 60% inhibition in the number of lung colonies compared with control, untreated animals. These results suggest that 2-ME may have clinical application for the treatment of pancreatic cancer.