Fig. 3

Response of A2780 and A2780cis to chronic hypoxia and hypoxia during treatment. a. A2780 cells exposed to chronic hypoxia before treatment with cisplatin resulted in a 10-fold increase in resistance when the treatment was also carried out in hypoxia. The resistance returned to that of normoxia when the chronically hypoxic cells were returned to normal oxygen for the treatment period. b. A2780cis displayed more modest changes in resistance (<2-fold) following hypoxia although this was still significant. c. Hypoxia naïve cells (cells not exposed to hypoxia before treatment) were exposed to hypoxia during cisplatin treatment for all or part of the 72 h treatment period for A2780. d. Hypoxia naïve cells (cells not exposed to hypoxia before treatment) were exposed to hypoxia during cisplatin treatment for all or part of the 72 h treatment period for and A2780cis. Both cell lines developed resistance when cells were challenged with cisplatin and hypoxia at the same time without any previous exposure, although the fold changes were more modest in A2780cis. e. Timecourse of HIF-1α protein expression (120 kDa). Loading control β-actin also shown (42 kDa). HIF-1α protein was absent in normoxia in A2780 and A2780cis. The levels fluctuated slightly over time, with an increase in HIF-1α expression at 3 days in A2780 and a decrease in HIF-1α expression in A2780cis at 3 days. A2780 cells were exposed to 50 μM CoCl₂ for 24 h for a positive control. n = 3 *p < 0.05 **p < 0.01 ***p < 0.001