3,3'-Diindolylmethane inhibits the invasion and metastasis of nasopharyngeal carcinoma cells in vitro and in vivo by regulation of epithelial mesenchymal transition.

Abstract

Nasopharyngeal carcinoma (NPC) is characterized by silent progression and atypical early symptoms. Early metastasis to the neck lymph nodes is common. However, conventional chemoradiotherapy is limited and unable to effectively control cervical lymph node metastasis of NPC. In addition, toxicities caused by chemoradiotherapy often induce damage to normal tissues and organs. Thus, the aim of this study was to investigate the ability of 3,3′-diindolylmethane (DIM) to inhibit the invasion and metastasis of NPC cells in vitro and in vivo. The migration and invasive abilities of the 5–8F human NPC cell line were detected using a Transwell assay. Lymph node metastasis in nude mice was observed following the implantation of xenograft tumors for 8 weeks. In addition, western blot analysis was used to detect the expression levels of epithelial mesenchymal transition (EMT)-associated key proteins in NPC cells treated with DIM in vitro and in vivo. The results demonstrated that DIM effectively inhibited the migration and invasion of NPC cells in vitro and the effect was concentration-dependent. In addition, DIM significantly delayed and reduced the occurrence of lymph node metastasis in the animal model. The expression levels of a number of key proteins associated with EMT were affected by DIM treatment. In the animal model, there were no signs of toxicity in the vital organs, including the heart, liver and kidney, of animals fed a diet containing DIM. Therefore, the results of the present study indicate that DIM affects the expression levels of a number of EMT-associated key proteins and induces the inhibition of invasion and metastasis of NPC cells in vitro and in vivo.