Quinalizarin enhances radiosensitivity of nasopharyngeal carcinoma cells partially by suppressing SHP-1 expression.

Xiaofen Pan, Rui Meng, Zhonghua Yu, Jingjing Mou, Sha Liu, Ziyi Sun, Zhenwei Zou, Gang Wu, Gang Peng

Index: Int. J. Oncol. 48 , 1073-84, (2016)

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Abstract

The purpose of this study was to investigate the influence of quinalizarin on the radiosensitivity of nasopharyngeal carcinoma (NPC) cells and the relevant underlying mechanisms. Human NPC cell lines CNE-1, CNE-2 and 5-8F were treated with quinalizarin and then irradiated with different X-rays doses. Cell viability, survival, DNA double-strand breaks (DSB), apoptosis, cell cycle distribution, expression of SHP-1 and other related proteins were detected with MTT assay, colony formation assay, immunofluorescent assay, flow cytometry and western blot analysis, respectively. We also examined how the effects of quinalizarin were affected by SHP-1-overexpression by lentivirus transfection. Quinalizarin at 25 µM enhanced radiosensitivity of NPC cells. This increased radiosensitivity was due to inhibition of cell viability, which delayed DSB repair as seen by significantly increased γ-H2AX foci, promoting apoptosis by 34% in CNE-1 and 9% in CNE-2 cells compared to controls and changing cell cycle distribution in CNE-1, but not CNE-2 cells. Quinalizarin treatment obviously decreased SHP-1 protein expression. Overexpressing SHP-1 partially reversed the radiosensitive effect of quinalizarin. Quinalizarin inhibited binding of p65 and the promoter of SHP-1, and decreased the activities of SHP-1 promoter and SHP-1. Quinalizarin enhanced radiosensitivity of NPC cells partially by suppressing SHP-1 expression.