Chen Danqing, Hackl Wolfgang, Ortmann Olaf, Treeck Oliver
Clinic for Obstetrics and Gynecology, University of Regensburg, Caritas Hospital St Josef, Regensburg, Germany.
Anticancer Drugs. 2004 Jan;15(1):55-61. doi: 10.1097/00001813-200401000-00009.
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.
依西美坦是一种非甾体类芳香化酶抑制剂，可阻断雌激素合成；紫杉醇是一种抗肿瘤药物，可抑制微管形成并干扰细胞增殖潜能，二者都是转移性乳腺癌的成熟治疗药物。鉴于依西美坦用于治疗预后较好的绝经后女性激素敏感性肿瘤，而紫杉醇通常用于治疗预后较差的激素不敏感型乳腺癌女性，目前尚无两种药物联合使用的经验。为了弄清楚依西美坦和紫杉醇同时使用时在多大程度上能增强彼此的疗效，评估了两种药物单独使用及联合使用对各种妇科肿瘤细胞系生长的影响。根据细胞滴度细胞增殖技术（也称为MTS测定法），通过测量相对细胞数量来测定肿瘤细胞生长。在表达芳香化酶的妇科癌细胞中，与依西美坦联合治疗可增强紫杉醇（10 nM）对细胞生长的作用。这种相加作用与雌激素受体α（ERα）表达无关，但依赖于雄烯二酮的存在。在HEC-1A和Ishikawa子宫内膜腺癌细胞以及SK-OV-3卵巢癌细胞和MDA-MB-231乳腺癌细胞中均观察到这种现象。我们的研究结果表明，紫杉醇与依西美坦联合使用可能对芳香化酶阳性的妇科癌症治疗有益，因为这可能使我们能够降低紫杉醇剂量，从而降低治疗的毒性。
