Histoprotective and antiproliferative effects of Raloxifene treatment during prostate carcinogenesis in rats

The ability of prostate cancer to progress to castration-resistant disease underscores the importance of study on adjuvant therapies. Recent research suggests estrogen receptors as possible therapeutic targets in neoplasias and they can be modulated by drugs such as Raloxifene. In this context, this study aimed to evaluate the effects of Raloxifene therapy during prostatic carcinogenesis through exposure to the carcinogen N-methyl-N-nitrosourea (MNU). To this end, male Fisher 344 rats underwent a tumor induction protocol using MNU (15 mg/kg), followed or not by treatment with Raloxifene (10 mg/kg). Raloxifene mitigated the tissue alterations induced by the tumor induction protocol by attenuating cell proliferation and the development of lesions, and by limiting their progression to malignancy. Additionally, the periacinar smooth muscle layer and the stromal distribution of collagen fibers were preserved in Raloxifene group. These results pointed to a protective role of Raloxifene on the prostatic microenvironment, attenuating the structural and proliferative alterations that accumulate during the carcinogenic process.