c regimen is chosen based on platinum suscepti bility but there is no established second line therapy. In the National Comprehensive Cancer Network guidelines, hormone therapy is classified under other drugs that are potentially effective as approved treatment for recurrent forms of epithelial ovarian cancer. However, the number of clinical and basic studies of hormone therapy conducted for this disease is insufficient. There is evidence that estrogen promotes proliferation of ovarian cancer in cell culture and a xenograft model. Furthermore, it has been shown that the growth of ovarian cancer cells is inhibited in vivo and in vitro by the anti estrogen therapy directed at estrogen receptor positive OVCAR 3 cells. There are two types of ER and ERB. ER is expressed in up to 60% of ovarian cancers.
ER activates expression of genes that are involved in cell survival and proliferation, whereas the function selleckchem BAPTA-AM of ERB has been found to be anti proliferative. Because the growth response in ovarian cancer cell lines is mediated by ER but not by ERB, treatment with an ER specific agonist trisphenol promotes cell proliferation. Aromatase converts adrenal androstenedione to estro gen and is expressed in fat, liver, muscle and cancers such as the breast and the ovary. Intra tumoral estrogens derived from in situ aromatization act as an autocrine growth factor that promotes cancer cell proliferation inde pendent of circulating estrogen. Aromatase inhibitors inhibit estrogen production in postmenopausal women by more than 90%. Expression of aromatase mRNA and the aromatase protein itself have been found in 33 81% of ovarian cancers.
The therapeutic effect of AIs has been shown to be superior to that of tamoxifen as adjuvant therapy for breast selleck cancer. In addition, in vitro studies showed an anti tumor effect of AI on ovarian cancer cells, which was associated with aromatase activity and ER expres sion. Letrozole is an oral non steroidal AI and used for the treatment of local or metastatic breast cancer that is ER positive. The present study was conducted to evaluate the effi cacy of letrozole in the late stages of ER positive ova rian cancer and elucidate the mechanism. Methods Cell cines and cell culture OVCAR 3 derived from human ovarian papillary adeno carcinoma and TOV 112D derived from human ovarian endometrioid adenocarcinoma were obtained from the American Type Culture Collection.
MCAS derived from human ovarian mucinous adeno carcinoma was obtained from Japanese Collection of Research Bioresources Cell Bank. DISS derived from human ovarian serous adenocarcinoma was kindly provided by Dr. Saga. All of these cell lines were grown in RPMI 1640 medium supplemented with 10% fetal bovine serum, 100 U ml penicillin and 100 ug ml streptomycin at 37 C in a water satura