Increased dexamethasone resistance of cystic fibrosis fibroblasts.

We demonstrate previously that fibroblasts from cystic fibrosis (CF) patients are significantly 
more resistant to the toxic effects of ouabain than normal human 
fibroblasts are. Ouabain is generally assumed to act primarily at the 
level of the cell membrane and to cause killing of cells 
by inhibiting ion transport. We have therefore examined the ability of 
normal and CF cells to survive exposure to ethacrynic acid, another 
inhibitor of ion transport, and to survive colchicine and aminopterin, resistance 
to which has been associated with membrane alterations in other cells. 
The effect of dexamethasone, which has a sterol nucleus similar to 
that of ouabain but is thought to have a different site 
of cellular action, was also tested. Exposure of the cells to 
ethacrynic acid, colchicine, or aminopterin did not reveal any differences in 
survival between normal and CF fibroblasts. However, CF cells survived exposure 
to dexamethasone significantly better than normal cells did. These results suggest 
that normal and CF cells do not differ in terms of 
a generalized resistance to ion transport inhibitors or to drugs that 
must pass through the membrane to be active. Instead, the results 
raise the possibility that CF cells have an enhanced resistance to 
drugs that have the sterol nucleus found in ouabain and dexamethasone. 
