TABLE 3

Potentiation of chemosensitivity by PKI166 in metastatic and MDR cells

Each cell line (4 × 103 cells/well) was treated with each anticancer drug for 96 h in the presence or absence of 0.5 μ M PKI166. Growth inhibition assay was performed by MTT method. Values in parentheses indicate the ratio of IC50 for drug alone to the IC50 for drug in the presence of PKI166. Data shown are the mean ± S.D. of two experiments carried out in triplicates. Results from a completely randomized design were analyzed with analysis of variance. The chemosensitizing effects of PKI166 were significantly higher in metastatic and MDR cells than in their respective drug-sensitive parental cells (P < 0.001).


Cells

Drugs

PKI166 Free

+ 0.5 μM PKI166
IC50
KM12 VP-16 (nM) 36 ± 2.4 20 ± 1.1 (1.8)
KM12SM 350 ± 12 80.4 ± 7.5 (4.4)
KM12L4A 310 ± 5 73.8 ± 5.0 (4.2)
A375 VP-16 15 ± 1.8 4.7 ± 0.3 (3.2)
A375SM 26 ± 1.5 2.0 ± 0.1 (13.0)
PC3 CPT (ng/ml) 2.1 ± 0.3 1.7 ± 0.03 (1.2)
PC3M-MM2 3.0 ± 0.2 0.6 ± 0.01 (5.0)
CEM VP-16 255 ± 18 230 ± 12 (1.1)
CPT 2.5 ± 0.2 0.4 ± 0.02 (6.3)
VBL (nM) 12 ± 1.7 10 ± 0.7 (1.2)
CEM/MDR VP-16 1300 ± 76 170 ± 10 (7.6)
CPT 1.6 ± 0.1 0.12 ± 0.01 (13.3)
VBL 210 ± 15.1 58 ± 3.2 (3.6)
MCF-7 VP-16 54 ± 1.8 50 ± 2.3 (1.1)
DOX (ng/ml) 3.2 ± 0.3 3.1 ± 0.1 (1.0)
MCF7/MDR VP-16 1400 ± 90 370 ± 22 (3.8)

DOX
35 ± 1.2
11 ± 0.8 (3.2)