v-Src–induced mitotic slippage confers resistance to microtubule-targeting agents.
A and B, HeLa S3/v-Src cells were treated with 10 μm STLC for 24 h with or without 2 ng/ml Dox for 24 h or 5 μm RO-3306 for 3 h at the end of the STLC treatment. Then, the cells were cultured in the medium without any drugs. A, phase-contrast images were obtained at 1 and 4 days after the removal of the drugs. B, DNA histograms of cells 11 days after the removal of the drugs are shown. Peak haploid genome equivalents (2N, 4N, and 8N) are indicated. Each curve represents 20,000 cells. C and D, HeLa S3/v-Src cells were treated with 0.1 μg/ml Taxol with or without 2 ng/ml Dox for 24 h. Then the cells were cultured in the medium without any drugs. C, phase-contrast images were obtained at the time indicated in the figure. D, viable cells were determined after culture for 2 days in the absence of Taxol and Dox by measuring the absorbance of water-soluble formazan at 450 nm. Relative absorbance is shown as a ratio to that of Dox-untreated cells with the mean ± S.D. from three independent experiments. The asterisks indicate a significant difference (**, p < 0.01) using Student's two-tailed t test.