Fig. 1.
In vitro antitumor activity of BSI-401 as a single agent. A, BSI-401 preferentially inhibits in vitro growth of PARP-1-expressing cells. On day 0, A12 (PARP-1−/−) and A16 (PARP-1+/+) MEF lines were seeded at a density of 1.0 × 103 cells/well. On the following day, the cells were treated with increasing doses of BSI-401. On day 2, the medium containing drugs was removed, the cells were washed twice with phosphate-buffered saline, and fresh medium was added. After 5 days of incubation, the relative variable cell numbers were determined. Dimethyl sulfoxide-treated cells were assigned a value of 0%. The means and SE of three independent experiments performed in triplicate are shown. B, Expression of PARP-1 and C, constitutive poly (ADP-ribosyl)ating activity in five different pancreatic cancer cell and MEF lines. D, BSI-401 cytotoxic activity on pancreatic cancer cell growth as a monolayer was determined as described above. E, BSI-401 inhibits low-anchorage tumor cell colony formation. On day 0, COLO357FG or MiaPaCa-2 cells (1.0 × 104 cells/well) were suspended in 0.6% soft agar. On day 1, cells were treated with increasing doses of BSI-401. After 14 days, photographs of fluorescent colonies were taken.