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.
Highlights
Nasopharyngeal carcinoma (NPC) is a common malignancy with a high metastatic and invasive rate that originates in the epithelial lining of the nasopharynx
NPC is sensitive to radiotherapy and chemotherapy, the majority of patients are diagnosed during the middle‐late stage and despite local lesions being well controlled, treatments for lymph node metastasis and local recurrence are limited
The results demonstrated that NPC cells treated with DIM had a decreased ability to migrate and invade
Summary
Nasopharyngeal carcinoma (NPC) is a common malignancy with a high metastatic and invasive rate that originates in the epithelial lining of the nasopharynx. Since NPC is radiosensitive, radiotherapy serves as the primary treatment, achieving 5‐year overall survival rates of 90 and 84% for early stage I and IIA NPC, respectively [4]. NPC is sensitive to radiotherapy and chemotherapy, the majority of patients are diagnosed during the middle‐late stage and despite local lesions being well controlled, treatments for lymph node metastasis and local recurrence are limited. A number of clinical studies [5,6] have found that the nodal status is an independent prognostic factor that affects the overall survival rate of NPC patients without distant metastasis. More effective treatment methods and drugs are required to effectively control lymph node metastasis and improve the overall survival rate [9]
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