TAMOXIFEN DELAYS THE DEVELOPMENT OF RESISTANCE TO CISPLATIN IN HUMAN-MELANOMA AND OVARIAN-CANCER CELL-LINES

The development of resistance to cisplatin (DDP) occurs rapidly both i n vitro and in vivo, and constitutes a major obstacle to effective the rapy. We have previously demonstrated that there is a highly synergist ic interaction between tamoxifen (TAM) and DDP against cell lines repr esentative of three different human cancers: melanoma, ovarian carcino ma and small-cell lung cancer. The purpose of these studies was to det ermine if TAM interferes with the development of resistance to DDP. T- 289 melanoma cells and 2008 ovarian cancer cells were cultured with in creasing concentrations of DDP +/- TAM in an attempt to induce resista nce to DDP. At various time points the cells were removed from culture and the degree of resistance to DDP was quantitated. Concurrent expos ure to TAM and DDP decreased both the rate and the absolute magnitude of resistance to DDP in both melanoma and ovarian cancer cell lines. I n the T-289 cell line the rate was decreased by a factor of 3.4 +/- 1. 4 (P <0.05), while in the 2008 cell line the rate was decreased by a f actor of 2.4 (P<0.01). TAM decreases the rate as well as the absolute magnitude of in vitro resistance to DDP in both melanoma and ovarian c ancer cell lines. These data suggest that the concurrent administratio n of TAM and DDP may result in a delay in the development of resistanc e to DDP which may have important clinical implications in the design of DDP-containing regimens.