Zaccheo T, Giudici D, Di Salle E
Laboratory of Endocrinology, R and D, Farmitalia Carlo Erba, Milano, Italy.
J Steroid Biochem Mol Biol. 1993 Mar;44(4-6):677-80. doi: 10.1016/0960-0760(93)90280-a.
The antitumor effect of exemestane (FCE 24304), an irreversible aromatase inhibitor, given alone or in combination with tamoxifen, was investigated in rats with 7,12-dimethylbenzanthracene (DMBA)-induced mammary tumors. The compounds were given once daily, 6 days a week for 4 weeks. Exemestane, given at the dose of 20 mg/kg/day s.c., induced 26% complete (CR) and 18% partial (PR) tumor regressions, compared to 0% CR and 6% PR observed in controls. Tamoxifen, given at 1 mg/kg/day p.o., induced 16% CR and 13% PR. The combined treatment caused 41% CR and 16% PR, thus resulting in a higher antitumor effect than either single treatment. The appearance of new tumors was reduced by each single treatment and almost totally prevented by the combined treatment. Serum prolactin (PRL) levels, assayed 4 h after the last dose, were unchanged in the group treated with the combination, whereas tamoxifen alone caused a slight increase of serum PRL. These results indicate that estrogen deprivation through aromatase inhibition and estrogen receptor antagonism causes a better inhibition of DMBA-induced mammary tumors than either treatment modality alone.
在7,12 - 二甲基苯并蒽（DMBA）诱导的乳腺肿瘤大鼠中，研究了不可逆芳香化酶抑制剂依西美坦（FCE 24304）单独使用或与他莫昔芬联合使用的抗肿瘤作用。这些化合物每周给药6天，每天一次，共给药4周。以20 mg/kg/天的剂量皮下注射依西美坦，诱导26%的肿瘤完全消退（CR）和18%的部分消退（PR），而对照组的CR为0%，PR为6%。以1 mg/kg/天的剂量口服他莫昔芬，诱导16%的CR和13%的PR。联合治疗导致41%的CR和16%的PR，因此产生了比单一治疗更高的抗肿瘤效果。每种单一治疗都减少了新肿瘤的出现，联合治疗几乎完全阻止了新肿瘤的出现。在最后一剂给药4小时后测定血清催乳素（PRL）水平，联合治疗组的血清PRL水平未发生变化，而单独使用他莫昔芬导致血清PRL略有升高。这些结果表明，通过芳香化酶抑制和雌激素受体拮抗作用剥夺雌激素，比单独使用任何一种治疗方式都能更好地抑制DMBA诱导的乳腺肿瘤。
