Inhibition of the Numb/Notch signaling pathway increases radiation sensitivity in human nasopharyngeal carcinoma cells.

Abstract

Radiation therapy is the primary treatment for primary nasopharyngeal carcinoma (NPC). The aim of this study is to identify the effect of the Numb/Notch signaling pathway on radiation sensitivity in human NPC cells. NPC tissues and normal nasopharyngeal tissues were collected. To evaluate the regulatory effects of the Numb/Notch signaling pathway, NPC cells were subjected to radiotherapy and various doses of the Numb/Notch signaling pathway inhibitor gamma secretase inhibitor (GSI). Next, the expression of Notch and Numb proteins was determined in NPC tissues and normal nasopharyngeal tissues, and the correlation of Notch and Numb protein expression with the clinicopathological features of NPC tissues was analyzed. Then, the effect of radiotherapy on NPC cell survival rate, survival fraction, apoptosis rate, proliferation, migration, and invasion as well as Numb/Notch signaling pathway-related molecules was detected. The results demonstrated that the Numb/Notch signaling pathway was activated in NPC tissues. Following treatment with radiotherapy and GSI, the Numb/Notch signaling pathway was inhibited. In addition, the NPC cell survival rate, survival fraction, cell proliferation, migration, and invasion were decreased, whereas the colony number and apoptosis rate were increased. Following radiotherapy and GSI treatment, Numb expression was increased, whereas Notch1, Hes1, Jagged1, and c-Myc expression was decreased. However, the greatest difference was noted upon treatment with radiotherapy +15 μM GSI. The results reported in this study suggest that a high dose of the inhibitor of the Numb/Notch signaling pathway GSI increased the radiation sensitivity in human NPC cells.