OBJECTIVE: To investigate the therapeutic mechanism of letrozole, the third-generation aromatase inhibitor, on endometriotic lesions in a rat model and its effect on the apoptosis of ectopic endometrial cells. METHODS: Endometriosis was induced by autotransplanting pieces of uterus onto the peritoneum in rats. The rats with successful ectopic implants were divided into 2 groups: A letrozole group (n=15) and a control group (n=15). The volume, appearance, and histopathology of ectopic implant were determined before and after the treatment. Expression of P450arom, COX-2, bcl-2, and bax in the ectopic implant was detected by immunohistochemistry and RT-PCR in the 2 groups. RESULTS: The volume of ectopic implant in the letrozole group was significantly reduced compared with the control group (P<0.05). The protein and mRNA levels of P450arom and COX-2 in the ectopic implant were significantly decreased in the letrozole group compared with the control group (P<0.05). There was a positive correlation between the expression of P450arom and the expression of COX-2 (r=0.943, P<0.001; r=0.913, P<0.001). The protein and mRNA expression of bcl-2 was significantly decreased (P<0.05), and the bax protein and mRNA expression was significantly increased (P<0.05) in the ectopic implant with an increased bax/bcl-2 ratio in the letrozole group compared with the control group (P<0.05). CONCLUSION Letrozole can obviously reduce the size of ectopic implant through decreasing P450arom and COX-2 expression, suppressing the secretion of estrogen, inhibiting the proliferation, and inducing the apoptosis of ectopic implants.
Animals ; Apoptosis ; drug effects ; Aromatase ; metabolism ; Aromatase Inhibitors ; therapeutic use ; Cyclooxygenase 2 ; metabolism ; Endometriosis ; drug therapy ; pathology ; Endometrium ; metabolism ; pathology ; Female ; Letrozole ; Nitriles ; therapeutic use ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Triazoles ; therapeutic use ; bcl-2-Associated X Protein ; metabolism