Effects of a combination of exemestane and paclitaxel on human tumor cells in vitro.

Abstract

Exemestane, a non-steroidal aromatase inhibitor that shuts down estrogen synthesis, and paclitaxel, an antineoplastic drug, inhibiting microtubule formation and interfering with the cells potential to proliferate, are well established treatments for metastatic breast cancer. Given that exemestane is a treatment for hormone-sensitive tumors in postmenopausal women with more favorable prognosis, while paclitaxel is normally used for women suffering from hormone-insensitive breast cancers with less favorable prognoses, there is currently no experience with the combination of the two drugs. In order to find out to what extent exemestane and paclitaxel add to each other's effects when given concomitantly, the effect of the two drugs alone and in combination on the growth of various gynecological tumor cell lines was assessed. Tumor cell growth was measured according to the cell titer cell proliferation technique, also referred to as the MTS assay, by measurement of relative cell numbers. In gynecological cancer cells expressing aromatase, the effect of a treatment with paclitaxel (10 nM) on cell growth was enhanced by co-treatment with exemestane. This additive effect was independent of ERalpha expression, but dependent on the presence of androstenedione. It was observed in HEC-1A and Ishikawa endometrial adenocarcinoma cells as well as in SK-OV-3 ovarian cancer and in MDA-MB-231 breast cancer cells. Our findings suggest that a combination of paclitaxel with exemestane might be beneficial for the treatment of aromatase-positive gynecological cancer, because it may allow us to reduce the paclitaxel dosage and therefore the toxicity of the treatment.