ANTIPROLIFERATIVE ACTIONS OF TAMOXIFEN TO HUMAN OVARIAN CARCINOMAS INVITRO

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (6) , 2266-2271
Abstract
The cytosolic estrogen receptor (ERc) and progestin receptor (PRc) levels were measured in 56 human epithelial ovarian tumors. The maximum ERc content in a tumor sample was 163 fmol/mg cytosolic protein while the maximum PRc content was 787 fmol/mg cytosolic protein. Of the tumor samples, 46 were evaluable for clonogenic growth in soft agar, and 19 samples produced 15 or more colonies per 105 cells plated. Four of the samples that grew had ERc levels of > 30 fmol/mg cytosolic protein. No correlation, however, between growth in soft agar and ERc, or PRc content was observed. The antiproliferative properties of the antiestrogen, tamoxifen, were studied. Although no decrease in colony formation was observed after a 1 h exposure to 0.2 or 2 .mu.M tamoxifen, continuous exposure of cells to 2 .mu.M tamoxifen reduced clonogenicity in 8 of 18 solid ovarian carcinomas examined. The maximum diminution in colony formation was .apprx. 50% of that of the control and was seen in 2 tumor samples. Both tumors that displayed the maximum response to continuous tamoxifen treatment had ERc and PRc levels > 30 fmol/mg cytosolic protein. None of the 14 tumors with ERc levels .ltoreq. 30 fmol/mg cytosolic protein exhibited a decrease in colony formation of > 50%. Exposure of cells for 1 h to the combination of doxorubicin and tamoxifen produced a significant antagonism of the individual doxorubicin or tamoxifen antiproliferative effects in 7 of 9 samples examined. In a subset of human ovarian epithelial carcinomas tamoxifen alone can have some direct antiproliferative action on the clonogenic cells. The maximum antiproliferative effect of tamoxifen observed was related to ERc content in ovarian tumors.