Enhanced in vivo targeting of estrogen receptor alpha signaling in murine mammary adenocarcinoma by nilotinib/rosuvastatin novel combination.

Enhanced in vivo targeting of estrogen receptor alpha signaling in murine mammary adenocarcinoma by nilotinib/rosuvastatin novel combination. Toxicol Appl Pharmacol. 2020 Aug 06;:115185 Authors: Goda AE, Elsisi AE, Sokkar SS, Abdelrazik NM Abstract The development of resistance to endocrine therapy of estrogen receptor alpha (ERα)-positive breast cancer is inevitable, necessitating the introduction of alternative treatment strategies. Therefore, the current study was carried out to investigate the in vivo efficacy and tolerability of nilotinib/rosuvastatin novel combination against ERα-positive breast carcinoma. Results showed that treatment of tumor-bearing mice with nilotinib/rosuvastatin exerted a significant antitumor activity. Mechanistically, the combination treatment efficiently inhibited the in vivo ERα protein expression, whereas ERα mRNA levels were unaffected suggesting a posttranslational regulation. In addition, the combination treatment markedly downregulated the expression of two ERα downstream target genes: C3 and pS2 confirming the inhibition of ERα signaling in vivo. Further, nilotinib/rosuvastatin combination strongly induced apoptosis evidenced by a marked caspase-3 cleavage and downregulation of tumor nitric oxide levels. Moreover, histopathology showed significant declines in mitotic figures and tumor giant cells implying the in vivo capability of the combination treatment to interfere with cancer cell pro...
Source: Toxicology and Applied Pharmacology - Category: Toxicology Authors: Tags: Toxicol Appl Pharmacol Source Type: research