Zoledronic Acid Restores Doxorubicin Chemosensitivity and Immunogenic Cell Death in Multidrug-Resistant Human Cancer Cells
Figure 4
Effects of ZA and inhibitors of ERK1/2, RhoA kinase, HIF-1α on MDR+ cells.
A. Phospho(Ser)-HIF-1α (pHIF-1α) and total HIF-1α expression in HMM cells left untreated (CTRL) or treated for 24 h at 10 µmol/L with the ERK1/2 kinase inhibitor PD98059 (PD), RhoA kinase inhibitor Y27632 (Y27), HIF-1α inhibitor YC-1 (YC), and 1 µmol/L ZA for 48 h. GAPDH data are shown to confirm equivalent per lane protein loading. B. HIF-1 activity in HMM cells left untreated (CTRL) or treated as reported in panel A. All differences between treated vs untreated cells are statistically significant (* p<0.01). C. Pgp expression in HMM cells of untreated (CTRL) and treated as reported in panel A. D. Intracellular doxorubicin concentrations in HMM cells in cells incubated as reported above in medium alone (CTRL), followed by 1 µmol/L Dox for a further 24 h. Differences between treated vs untreated cells are statistically significant (*p<0.01). Results shown in panels A and C are representative data from one of 2 experiments. For panels B and D, the results represent the mean ± SD of 3 independent experiments.