Analysis of the Ki-67 index in the vaginal epithelium of castrated rats treated with tamoxifen

Abstract

OBJECTIVES:Vaginal atrophy and breast cancer are common conditions in postmenopausal women and tamoxifen is the standard endocrine treatment for hormone-sensitive tumors. The present study aimed to assess the effect of tamoxifen on Ki-67 protein expression in the vaginal epithelium of castrated rats.MATERIAL AND METHODS:Forty Wistar-Hannover adult, virgin, castrated rats were randomly divided into two groups, group I (control, n=20) and group II (tamoxifen, n=20), receiving 0.5 ml of propylene glycol and 250 µg of tamoxifen diluted in 0.5 ml of propylene glycol, respectively, daily by gavage for 30 days. On the 31st day, the rats were euthanized and their vaginas were removed and fixed in 10% buffered formalin for the immunohistochemical study of Ki-67 protein expression. Data were analyzed by the Levene and Student's t tests (p<0.05).RESULTS:The mean index of Ki-67 expression in the rat vagina of groups I and II was 4.04±0.96 and 26.86±2.19, respectively (p<0.001).CONCLUSIONS:According to the results of the present study, tamoxifen, at the dose and treatment length used, induced a significant increase in the cell proliferation of the vaginal mucosa in castrated rats, as evaluated by Ki-67 protein expression.

Effects of anastrozole on Ki-67 antigen expression in the vaginal epithelium of female rats in persistent estrus

“…Nevertheless, the effects of anastrozole administered by oral gavage to premenopausal rats, as opposed to oral exposure in the diet, are unknown. Meanwhile, Nery-Aguiar et al (1) administered tamoxifen to castrated female rats, mimicking postmenopausal women, which increased proliferation in the vaginal epithelium. On the other hand, Sousa-Lages et al (25) did not show alterations in the vaginal epithelium of castrated female rats with the use of pilocarpine, a cholinergic parasympathomimetic agonist that induces an increase in glandular secretion and with controversial effects on vaginal dryness.…”

“…Vaginal atrophy and hormone-sensitive breast cancer are common conditions in postmenopausal women, for which tamoxifen is the standard endocrine therapy; however, although tamoxifen may have trophic effects on the vaginal epithelium, severe adverse effects such as endometrial cancer lead to the search of alternative endocrine therapies (1). Third-generation aromatase inhibitors, such as anastrozole, letrozole, and exemestane, have become the first-choice drug for endocrine treatment of hormone-sensitive breast cancer in postmenopausal women.…”

“…to study the effects of hormonal drugs (15)(16), such as anastrozole, which inhibit estrogen synthesis. Nery-Aguiar et al (1) showed that tamoxifen significantly increased cell proliferation in the vaginal mucosa of castrated rats, as evaluated by means of Ki-67 protein expression. On the other hand, the effects of anastrozole in the vaginal epithelium of premenopausal rats are unclear.…”