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Antiproliferative Actions of Tamoxifen to Human Ovarian Carcinomas in Vitro¹

Departments of Pharmacology [J. S. L., N. J. M., A. J. E.] and Obstetrics and Gynecology [P. E. S., N. J. M., D. C. L., A. J. E.], Yale University School of Medicine, New Haven, Connecticut 06510

The cytosolic estrogen receptor (ER_c) and progestin receptor (PR_c) levels were measured in 56 human epithelial ovarian tumors. The maximum ER_c content in a tumor sample was 163 fmol/mg cytosolic protein while the maximum PR_c content was 787 fmol/mg cytosolic protein. Forty-six of the tumor samples 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 ER_c levels of >30 fmol/mg cytosolic protein. No correlation, however, between growth in soft agar and ER_c or PR_c content was observed. The antiproliferative properties of the antiestrogen, tamoxifen, were studied. Although no decrease in colony formation was observed after a 1-hr exposure to 0.2 or 2 µM tamoxifen, continuous exposure of cells to 2 µM tamoxifen reduced clonogenicity in 8 of 18 solid ovarian carcinomas examined. The maximum diminution in colony for mation was approximately 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 ER_c and PR_c levels >30 fmol/mg cytosolic protein. None of the 14 tumors with ER_c levels 30 fmol/mg cytosolic protein exhibited a decrease in colony formation of more than 50%. Exposure of cells for 1 hr 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. These data suggest that 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 ER_c content in ovarian tumors.

¹ This work was supported by USPHS Grant CA-08341.

² To whom requests for reprints should be addressed, at Department of Pharmacology, P.O. Box 3333, 333 Cedar Street, Yale University, New Haven, CT 06510.

Received 1/31/83. Accepted 2/22/84.