Naloxone Counteracts the Promoting Tumor Growth Effects Induced by Morphine in an Animal Model of Triple-negative Breast Cancer

Abstract

Background/Aim: Our group has previously demonstrated, in in vitro and in vivo studies on triple-negative breast cancer, that morphine promoted breast cancer progression whereas naloxone was able to reduce it. In this subsequent investigation, we aimed to assess the combinatorial effects of these two drugs in an animal model of triple negative breast cancer. Materials and Methods: In order to evaluate the in vivo effects of the combination of morphine and naloxone in human breast cancer, a mouse model of human triple-negative breast cancer was generated by injecting the MDA-MB-231 cells subcutaneously in nude mice. Naloxone and morphine were daily intraperitoneally co-injected in mice for 4 weeks at two different doses. Micro-vessel formation was detected by fluorescein isothiocyanate-dextran (100 μl) injected into the lateral tail vein of mice and confirmed by immunohistochemistry for PECAM-1 on mice tumor sections. Results: In vivo experiments showed that naloxone was able to counteract the promoting effects of morphine on tumor growth. No impairment of micro-vessel formation in tumors of mice treated with the two drugs was observed. Conclusion: Herein, we demonstrated that naloxone was able to counteract the promoting effects of morphine on tumor growth without impairing micro-vessel formation.