Table 1.
Cell proliferation was determined by SRB assay as described in Materials and Methods. Data are presented as means ± SDs from at least three independent experiments performed in quadruplicate. The fold reversal of resistance was calculated by dividing the IC50 for mitoxantrone (Top Panel) or cisplatin (Bottom Panel) in the absence of PPARγ agonist by that obtained in the presence of PPARγ agonist. The specific ABCG2 inhibitor, FTC, was used as the positive control. The three PPARγ agonists when tested alone, telmisartan, pioglitazone and rosiglitazone, did not affect cell proliferation at concentrations below 20 μM, 5 μM and 60 μM respectively.
| IC50 ± SD (fold reversal) | ||||
|---|---|---|---|---|
| MCF-7 | MCF-7 FLV1000 (ABCG2-overexpression) | HEK293/pcDNA3 (stably transfected) | HEK293/ABCG2 (stably transfected) | |
| Mitoxantrone alone | 0.0097 ± 0.0035 μM | 2.116 ± 0.261 μM | 0.83 ± 0.42 nM | 46.2 ± 3.5 nM |
| +FTC 5 μM | 0.0100 ± 0.0021 μM (1.0) | 0.023 ± 0.010 μM (92) | 0.79 + 0.37 nM (1.1) | 1.08 ± 0.36 nM (42.8) |
| +Telmisartan 1 μM | 0.0152 ± 0.0251 μM (0.6) | 0.378 ± 0.101* μM (5.6) | 1.42 ± 0.69 nM (0.6) | 28.8 ± 6.9 nM (1.6) |
| +Telmisartan 2 μM | 0.0087 ± 0.0022 μM (1.1) | 0.168 ± 0.038* μM (12.6) | 1.80 ± 0.72 nM (0.5) | 9.6 ± 2.1* nM (4.8) |
| +Telmisartan 10 μM | 0.0110 ± 0.0260 μM (0.9) | 0.048 ± 0.035* μM (44.1) | 1.08 ± 0.63 nM (0.8) | 1.6 ± 0.5* nM (28.9) |
| +Pioglitazone 1 μM | 0.0109 ± 0.0312 μM (0.9) | 1.519 ± 0.253 μM (1.4) | 0.94 ± 0.52 nM (0.9) | 35.2 ± 5.4 nM (1.3) |
| +Pioglitazone 2 μM | 0.0081 ± 0.0045 μM (1.2) | 0.369 ± 0.062* μM (5.7) | 0.88 ± 0.49 nM (0.9) | 24.1 ± 3.6 nM (1.9) |
| +Pioglitazone 5 μM | 0.0042 ± 0.0044 μM (2.3) | 0.162 ± 0.031* μM (13.1) | 1.12 ± 0.46 nM (0.7) | 10.5 ± 2.8* nM (4.4) |
| +Rosiglitazone 1 μM | 0.0126 ± 0.0035 μM (0.8) | 0.175 ± 0.032* μM (12.1) | 0.86 ± 0.26 nM (1.0) | 29.5 ± 3.2 nM (1.6) |
| +Rosiglitazone 10 μM | 0.0082 ± 0.0041 μM (1.2) | 0.119 ± 0.031* μM (17.8) | 1.19 ± 0.35 nM (0.7) | 9.2 ± 2.4* nM (5.0) |
| +Rosiglitazone 50 μM | 0.0039 ± 0.0042 μM (2.5) | 0.095 ± 0.021* μM (22.3) | 1.18 ± 0.48 nM (0.7) | 4.8 ± 1.0* nM (9.6) |
| Cisplatin alone | 11.23 ± 2.11 μM | 12.45 ± 1.43 μM | 2.02 ± 0.34 μM | 2.15 ± 0.86 μM |
| +FTC 5 μM | 12.56 ± 1.87 μM (1.0) | 11.98 ± 1.37 μM (1.0) | 1.99 ± 0.36 μM (1.0) | 2.35 ± 0.76 μM (0.9) |
| +Telmisartan 2 μM | 10.98 ± 1.87 μM (1.0) | 13.15 ± 2.11 μM (0.9) | 2.26 ± 0.65 μM (0.9) | 1.98 ± 0.74 μM (1.1) |
| +Telmisartan 10 μM | 11.25 ± 2.09 μM (1.0) | 12.78 ± 1.88 μM (1.0) | 2.19 ± 0.49 μM (0.9) | 2.05 ± 0.68 μM (1.0) |
| +Pioglitazone 2 μM | 10.76 ± 2.02 μM (1.0) | 11.67 ± 1.54 μM (1.1) | 1.86 ± 0.59 μM (1.1) | 2.11 ± 0.48 μM (1.0) |
| +Pioglitazone 5 μM | 12.98 ± 1.72 μM (0.9) | 12.19 ± 1.76 μM (1.0) | 2.01 ± 0.43 μM (1.0) | 1.98 ± 0.56 μM (1.1) |
| +Rosiglitazone 10 μM | 11.76 ± 2.14 μM (1.0) | 12.64 ± 1.76 μM (1.0) | 1.59 ± 0.86 μM (1.3) | 2.08 ± 0.59 μM (1.0) |
| +Rosiglitazone 50 μM | 10.88 ± 1.65 μM (1.0) | 11.54 ± 1.28 μM (1.1) | 1.89 ± 0.46 μM (1.1) | 2.16 ± 0.47 μM (1.0) |
*
P < 0.05, versus that obtained in the absence of inhibitor