Tamoxifen delays the development of resistance to cisplatin in human melanoma and ovarian cancer cell lines.

Ef Mcclay,Ja Jones,Kd Albright,Sb Howell,Rd Christen

doi:10.1038/bjc.1994.326

Ef Mcclay, Ja Jones + Show 3 more

Open Access

https://doi.org/10.1038/bjc.1994.326

Copy DOI

Abstract

The development of resistance to cisplatin (DDP) occurs rapidly both in vitro and in vivo, and constitutes a major obstacle to effective therapy. We have previously demonstrated that there is a highly synergistic interaction between tamoxifen (TAM) and DDP against cell lines representative of three different human cancers: melanoma, ovarian carcinoma and small-cell lung cancer. The purpose of these studies was to determine if TAM interferes with the development of resistance to DDP. T-289 melanoma cells and 2008 ovarian cancer cells were cultured with increasing concentrations of DDP +/- TAM in an attempt to induce resistance to DDP. At various time points the cells were removed from culture and the degree of resistance to DDP was quantitated. Concurrent exposure to TAM and DDP decreased both the rate and the absolute magnitude of resistance to DDP in both melanoma and ovarian cancer cell lines. In 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 factor 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 cancer cell lines. These data suggest that the concurrent administration of TAM and DDP may result in a delay in the development of resistance to DDP which may have important clinical implications in the design of DDP-containing regimens.

Highlights

We report here that TAM can delay the development of DDP resistance in both T-289 and 2008 cells when given concurrently with DDP in cell culture
The T-289 melanoma cell line was derived from a tumour explant of a patient and has been passaged for >7 years (Taetle et al, 1987)
The 2008 cell line is an ovarian carcinoma line derived from a patient with an ovarian serous cystadenocarcinoma (Andrews et al, 1988)

Summary

Cell lines and culture

The T-289 melanoma cell line was derived from a tumour explant of a patient and has been passaged for >7 years (Taetle et al, 1987). The 2008 cell line is an ovarian carcinoma line derived from a patient with an ovarian serous cystadenocarcinoma (Andrews et al, 1988). Cells were cultured in 75 cm flasks (Corning, Corning, NY, USA) in RPMI-1640 (Irving Scientific, Santa Ana, CA, USA) supplemented with 10% fetal bovine serum, 50figml-' gentamicin (Gemini Bio-Products, Calabasa, CA, USA), 2 mM L-glutamine, 10 nM hydrocortisone, 5 fg ml-' insulin, 5 jg ml'. Human transferrin, 10 nM oestradiol and 5 ng ml-' selenium (Sigma, St Louis, MO, USA)

Drugs and chemicals

Induction of DDP resistance

Findings

Colony formation assay