In vitro response of a human colon tumor xenograft and a lung adenocarcinoma cell line to alpha-difluoromethylornithine alone and in combination with 5-fluorouracil and doxorubicin

We have investigated effects of alpha-difluoromethylornithine (DFMO), both as a single agent and in combination with 5-fluorouracil (5-FU) against a human colon tumor xenograft (T6) grown as primary tissue culture in serum-free medium and in combination with doxorubicin (DX) against a human lung adenocarcinoma cell line (A549). DFMO showed a dose-dependent growth-inhibitory effect against human colon tumor xenograft and lung adenocarcinoma cells. Growth-inhibitory activity of DFMO against T6 cells was reversed completely when the cells were treated simultaneously with putrescine (PU) (10(-6) M) and DFMO (10(-3) M). When 5-FU and DFMO were used in combination against T6 cells, no antagonism or synergism between the two drugs was seen. However, in the case of A549 cells, when DFMO was used in combination with DX, there was a consistent increase in growth inhibition that surpassed the inhibition of either agent given alone.