Letrozole (CGS 20267) is an orally active nonsteroidal selective aromatase inhibitor with an IC50 of 11.5nM[1]. Letrozole prevents aromatase from producing estrogens by competitively and reversibly binding to the heme of its cytochrome P450 unit[2]. Letrozole is commonly used to treat certain types of breast cancer in postmenopausal women, including hormone receptor-positive breast cancer[3].
In vitro, Letrozole (100nM) treatment of breast cancer MCF7 cells for 72h significantly reduced the migration, invasion and adhesion of MCF7 cells when co-cultured with cancer-associated fibroblasts (CAFs), but had no effect on the proliferation of MCF7 cells[4]. Letrozole (10nM) treatment of breast cancer MCF7 cells for 24h and 48h significantly inhibited the levels of intracellular matrix metalloproteinases (MMPs) and also inhibited the stimulatory effect of testosterone on the proliferation of MCF7 cells[5].
In vivo, oral administration of Letrozole (1, 2.5mg/kg/day) to male Parkes mice for 28 days showed degenerative changes in the testicular histology of the mice, a significant decrease in the number of PCNA-positive germ cells in each seminiferous tubule in the testis, a significant increase in testosterone levels, but a significant decrease in estradiol levels[6]. Oral administration of Letrozole (0.5mg/kg/day) to rats with endometriosis for 3 weeks significantly reduced the size of the endometriosis, with a reduction percentage of 79.92% ± 7.89%[7].
References:
[1] Bhatnagar A S, Häusler A, Schieweck K, et al. Highly selective inhibition of estrogen biosynthesis by CGS 20267, a new non-steroidal aromatase inhibitor[J]. The Journal of steroid biochemistry and molecular biology, 1990, 37(6): 1021-1027.
[2] Miller W R, Bartlett J, Brodie A M H, et al. Aromatase inhibitors: are there differences between steroidal and nonsteroidal aromatase inhibitors and do they matter?[J]. The oncologist, 2008, 13(8): 829-837.
[3] Barnadas A, Estévez L G, Lluch-Hernández A, et al. An overview of letrozole in postmenopausal women with hormone-responsive breast cancer[J]. Advances in therapy, 2011, 28: 1045-1058.
[4] Li K, Kang H, Wang Y, et al. Letrozole-induced functional changes in carcinoma-associated fibroblasts and their influence on breast cancer cell biology[J]. Medical Oncology, 2016, 33: 1-11.
[5] Mitropoulou T N, Tzanakakis G N, Kletsas D, et al. Letrozole as a potent inhibitor of cell proliferation and expression of metalloproteinases (MMP‐2 and MMP‐9) by human epithelial breast cancer cells[J]. International journal of cancer, 2003, 104(2): 155-160.
[6] Verma R, Krishna A. Effect of Letrozole, a selective aromatase inhibitor, on testicular activities in adult mice: Both in vivo and in vitro study[J]. General and Comparative Endocrinology, 2017, 241: 57-68.
[7] Yarmolinskaya M, Molotkov A. Evaluation of the effectiveness of letrozole in the treatment of experimentally modeled endometriosis in rats[J]. Journal of Endometriosis and Pelvic Pain Disorders, 2019, 11(3): 126-131.
Letrozole（来曲唑; CGS 20267）是一种口服活性非甾体类选择性芳香酶抑制剂，IC50为11.5nM[1]。Letrozole通过与其细胞色素P450单元的血红素竞争性、可逆结合来防止芳香酶产生雌激素[2]。Letrozole通常用于治疗绝经后女性的某些类型的乳腺癌，包括激素受体阳性乳腺癌[3]。
在体外，Letrozole（100nM）处理乳腺癌MCF7细胞72h，在与癌相关成纤维细胞（CAFs）共培养的条件下，Letrozole显著降低了MCF7细胞的迁移、侵袭和粘附，但对MCF7细胞的增殖没有影响[4]。Letrozole（10nM）处理乳腺癌MCF7细胞24h和48h，显著抑制了细胞内基质金属蛋白酶（MMP）的水平，还抑制睾酮对MCF7细胞增殖的刺激作用[5]。
在体内，Letrozole（1, 2.5mg/kg/day）通过口服治疗雄性Parkes品系小鼠28天，小鼠睾丸组织学出现退行性改变，睾丸内每个曲细精管的PCNA阳性生殖细胞数量明显减少，睾酮水平明显升高，但雌二醇水平明显下降[6]。Letrozole（0.5mg/kg/day）通过口服治疗子宫内膜异位症大鼠3周，显著减小了异位症大小，减少百分比为79.92%±7.89%[7]。