Table II.
Effect of P-gp inhibitors and ABCG2 inhibitors on sunitinib resistance in HMEC-1 cells.
| HMEC-1 | HMECd1 | HMECd2 | |||||
|---|---|---|---|---|---|---|---|
|
|
|
|
|||||
| Agents | IC50, μM | IC50, μM | RI | RF | IC50, μM | RI | RF |
| Sunitinib | 4.271±0.501 | 8.585±0.642 | 2.01a | 1.00 | 19.252±0.855 | 4.51a | 1.00 |
| + 5 μM fumC | 4.359±0.622 | 5.886±0.417 | 1.35b | 1.45 | 6.163±0.062 | 1.41b | 3.12 |
| + 0.5 μM die | 4.204±0.468 | 6.259±0.541 | 1.48b | 1.37 | 7.159±0.057 | 1.70b | 2.69 |
| + 1 μM vrp | 4.952±0.875 | 9.159±0.356 | 1.84 | 0.94 | 17.659±0.526 | 3.57 | 1.09 |
| + 2.5 μM cysA | 4.098±0.562 | 8.871±0.459 | 2.16 | 0.97 | 20.348±0.328 | 4.97 | 0.95 |
The cells were treated as described in the main text and tested with MTS assay. The RI was determined by: IC50 of Dox-treated HMECd1 or HMECd2 cells/IC50 of Dox-treated HMEC-1 cells. The RF was calculated by: IC50 of Dox-treated HMECd1 or HMECd2 cells/IC50 of the same cell line treated by sunitinib + P-gp or ABCG2 inhibitors.
P<0.05, vs. HMEC-1 cells;
P<0.05, vs. HMECd1 and HMECd2 cells without P-gp or ABCG2 inhibitors.
P-gp, P-glycoprotein; ABCG2, breast cancer resistance protein; RI, resistance index; RF, resistance fold; IC50, half maximal inhibitory concentration; Dox, doxorubicin; fumC, fumitremorgin C; die, diethylstilbestrol; vrp, verapamil; cysA, cyclosporine A.