Figure 2. The impact of pulsed drug treatment on long-term cell growth and death.

Examples of long-term growth curves for cells incubated with either gemcitabine or cisplatin are shown. In both cases, asynchronously growing MDA-MB-231 breast cancer cells were incubated with drug at the indicated concentrations for 6 h, then the drug was removed, and the cells allowed to repair, grow, and/or die over the following 8 days. The experiment was performed in a 96-well format and DNA content was assessed at each time point [14]. By starting with sufficient cells/well, and harvesting a plate on day 0, the starting DNA content can be assessed. The growth rate of untreated cells is limited as the wells rapidly reach high cell density, and cells whose growth is partially inhibited will eventually attain the same cell number as controls. Cells incubated with either 150 nM gemcitabine or 20 - 40 µM cisplatin exhibit curves that would be considered “stable disease” in a patient. Higher concentrations of both drugs clearly caused a decrease in cell number, but this was not observed until 6 or 4 days following gemcitabine or cisplatin, respectively.