Journal of Cancer Therapy, cilt.16, sa.8, ss.259-286, 2025 (Hakemli Dergi)
Objective: This study investigates the effects of tamoxifen, a selective estrogen receptor modulator, and letrozole, an aromatase inhibitor, on the endometrium in a rat model. It further evaluates the combined impact of these drugs with acetylsalicylic acid (aspirin), a non-selective COX inhibitor, through immunohistochemical and biochemical analyses, aiming to compare endometrial alterations and the potential mitigating effects of aspirin. Methods: Seventy female rats were divided into seven groups receiving tamoxifen, letrozole, their combinations with aspirin, and control treatments. Endometrial tissues were analyzed for VEGF, COX-2, Ki-67, BCL-2, and PECAM-1 expression using immunohistochemistry, while serum VEGF-C levels were quantified via ELISA. Statistical comparisons were conducted across groups. Results: Tamoxifen significantly increased VEGF and COX-2 expression in the endometrium compared to controls, whereas aspirin co-administration significantly reduced these levels. No significant Ki-67 expression changes were observed in the glandular epithelium or stroma. Tamoxifen did not affect BCL-2 expression in the epithelium but decreased stromal expression. PECAM-1 expression remained unchanged across groups, and tamoxifeninduced serum VEGF-C elevation was not statistically significant. Conclusions: Tamoxifen increases VEGF and COX-2 expression, potentially contributing to endometrial pathologies, while aspirin co-administration effectively mitigates these effects, suggesting its protective role against uterine complications. Letrozole demonstrated minimal endometrial impact, reinforcing its favorable safety profile. The combination of tamoxifen and aspirin may represent a viable strategy to alleviate endometrial side effects in clinical applications.