Cellular Redox Status Regulates Emodin-Induced Radiosensitization of Nasopharyngeal Carcinoma Cells In Vitro and In Vivo.

Huaxin Hou,Danrong Li,Yi Zhou,Li Li,Daohai Cheng,Ying Liu

doi:10.1155/2013/218297

Abstract

Here, we report that regulation of cellular redox status is required for radiosensitization of nasopharyngeal carcinoma (NPC) cells by emodin. We evaluated emodin's radiosensitivity-enhancing ability by using NPC cells in vitro and xenografts in vivo. A clonogenic assay was performed to evaluate NPC cell survival and to determine dose modification factors. Flow cytometry, western blot analysis, and in vivo radiation-induced tumor regrowth delay assays were performed to characterize emodin's effects. Exposure of CNE-1 NPC cells to emodin enhanced their radiosensitivity. HIF-1α expression significantly increased under hypoxic conditions but did not change after treatment with emodin alone. Emodin downregulated mRNA and protein expression of HIF-1α. Cells exposed to radiation and emodin underwent significant cell cycle arrest at the G2/M phase. The percentage of apoptotic cells and reactive oxygen species (ROS) levels were significantly higher in the group exposed to emodin and radiation hypoxic group than in the other groups. Compared to the CNE-1 xenografts exposed to radiation alone, CNE-1 xenografts exposed to radiation with emodin showed significantly enhanced radiation effects. Our data suggest that emodin effectively enhanced the radiosensitivity of CNE-1 cells in vitro and in vivo. The mechanism appears to involve ROS generation and ROS-mediated inhibition of HIF-1α expression.

Highlights

One of the most common types of head and neck cancer is nasopharyngeal carcinoma (NPC), a highly metastatic, invasive, and malignant cancer that shows a marked geographic and racial distribution
No cytotoxicity was observed in CNE-1 cells provided that the concentration of emodin was kept lower than 62.5 μg/mL, where the inhibitory ratio was less than 10%
Hypoxia in tumors is generally associated with radioresistance, mainly because such therapies require adequate intratumoral oxygen to be maximally cytotoxic

Summary

Introduction

One of the most common types of head and neck cancer is nasopharyngeal carcinoma (NPC), a highly metastatic, invasive, and malignant cancer that shows a marked geographic and racial distribution. The majority of patients diagnosed with NPC undergo radiation therapy, but some patients receiving radiation present with local tumor recurrence and distant metastases after radiotherapy. This is believed to be caused by radioresistance, and the majority of these patients exhibit tumor recurrence and metastasis within 1.5 years after completion of the treatment regimen. Tumor hypoxia has become an obstacle for both chemotherapy and radiotherapy. An increasing number of studies show that the bioreductive agent emodin

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Conclusion