Human nasopharyngeal carcinoma can be radiosensitized by trichosanthin via inhibition of the PI3K pathway

Exp Ther Med. 2018 Nov;16(5):4181-4186. doi: 10.3892/etm.2018.6719. Epub 2018 Sep 11.

Abstract

Nasopharyngeal carcinoma (NPC) is a prevalent tumor that affects the head and neck. Radiation therapy is typically used to treat NPC; however, poor prognoses and distant metastases are common due to radiation resistance. The antitumor activities of trichosanthin (TCS) have been reported in several types of tumors. The aim of the present study was to investigate whether TCS may serve as a potential radiosensitizer in the treatment of NPC tumors. In the present study, NPC cells were treated with radiation alone or together with TCS and radiosensitivity was compared. Clonogenic assay, flow cytometry and an animal study were performed to assess cell death in NPC. The clonogenic assay demonstrated that TCS had a significant radiosensitizing effect on NPC cells. Western blotting indicated that phosphorylated protein kinase B and signal-regulated kinase [phosphoinositide 3-kinase (PI3K) pathway] were downregulated, and that cleaved caspase-3 was upregulated by combined treatment with TCS and radiation. Furthermore, TCS potently radiosensitized NPC xenografts in vivo. In conclusion, TCS radiosensitized NPC in vitro and in vivo via downregulation of PI3K pathways and the upregulation of cleaved caspase-3.

Keywords: nasopharyngeal carcinoma tumor; phosphoinositide 3-kinase pathway; radiosensitivity; trichosanthin.