The effect of adriamycin and 4'-deoxydoxorubicin on cell survival of human lung tumour cells grown in monolayer and as spheroids.
Kerr DJ., Wheldon TE., Kerr AM., Freshney RI., Kaye SB.
Using growth delay and clonogenic cell survival as end points, we have shown that the 3-dimensional structure of human lung tumour spheroids confers a degree of resistance to the anthracyclines adriamycin and 4'-deoxydoxorubicin, relative to cells grown as monolayer. 4'-deoxydoxorubicin induces a longer growth delay and greater clonogenic cell kill than adriamycin in spheroids, although it is no more cytotoxic in monolayer (exponential and plateau phase). There is a log linear relationship between clonogenic cell survival and duration of adriamycin exposure in monolayers, and biphasic curve with a lesser degree of cell kill for disaggregated spheroid cells. Using fluorescent microscopy we have demonstrated, qualitatively, that the more lipophilic analogue partitions into the spheroid more rapidly and to a greater degree than adriamycin. It is possible that adriamycin penetration is a relatively important aspect of spheroid drug resistance, which may be related to intraspheroidal pH gradients, and that we have partially overcome this by using a lipophilic analogue.