Low-dose naltrexone inhibits the epithelial-mesenchymal transition of cervical cancer cells in vitro and effects indirectly on tumor-associated macrophages in vivo

Abstract

The metastasis of cervical cancer has always been a clinical challenge. We investigated the effects of low-dose naltrexone (LDN) on the epithelial mesenchymal transition of cervical cancer cells in vitro as well as its influence on macrophage polarization and associated cytokines in vivo. The results suggested that LDN supressed the proliferation, migration and invasion abilities and promote their apoptosis in Hela cells, whereas the opioid growth factor receptor (OGFr) silenced significantly reversed these effects in vitro. Knockdown the expression of OGFr, the inhibitory of LDN on EMT was weakened. LDN could inhibit cervical cancer progression in nude mice. In additon, LDN indirectly reduced the number of tumor-associated macrophages (TAMs), mainly M2 macrophages, and decreased expression of anti-inflammatory factor IL-10 in the serum of nude mice. These findings demonstrate that LDN could be a potential treatment for cervical cancer.

Keywords: Cervical cancer; Epithelial-mesenchymal transition (EMT); Low-dose naltrexone (LDN); Opioid growth factor receptor (OGFr); Tumor-associated macrophages (TAMs).