Triptolide inhibits cell growth and GRP78 protein expression but induces cell apoptosis in original and radioresistant NPC cells

// Chengmin Li 1, * , Bin Zhang 2, * , Wuwu Lv 1 , Chen Lai 3 , Zhikang Chen 3 , Ran Wang 3 , Xueying Long 4 , Xueping Feng 1 1 Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China 2 Department of Histology and Embryology, Xiangya School of Medicine, Central South University, Changsha, Hunan Province 410008, China 3 Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China 4 Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China * These authors contributed equally to this work Correspondence to: Xueping Feng, email: fxp1029@aliyun.com Keywords: nasopharyngeal carcinoma, CNE2, radioresistance, triptolide, GRP78 Received: November 05, 2015 Accepted: June 16, 2016 Published: July 06, 2016 ABSTRACT The radioresistance is the key factor to hamper curative effect and survival of nasopharyngeal carcinoma (NPC) patients. Nature triptolide (TPL) has been found to circumvent drug-resistant effect of cancer, but its effect on NPC radioresistance has been rarely studied. In the present study, the 10 Gy-resistant CNE2 subclones (CNE2-SR) were used as a NPC radioresistant model. The IC 50 of TPL in CNE2 and CNE2-SR cells was measured by MTT assay, cell cycle was analyzed by flow cytometry, and protein expression was examined by western blot. Our data showed that TPL treatment decreased the percentage of viable cells, and IC50 value in CNE2 and CNE2-SR cells was 23.6 ± 1.41 nmol/L and 31.2 ± 1.16 nmol/L, respectively. Six Gy was a moderate dosage of X-ray for CNE2, and 25 nM TPL was close to IC50 value of CNE2 and CNE2-SR. Six Gy X-ray and/or 25 nM TPL significantly inhibited tumor growth in nude mice. Furthermore, 6 Gy X-ray and/or 25 nM TPL significantly inhibited cell growth and induced cell apoptosis and M/G2 phase arrest in CNE2 and CNE2-SR cells. Moreover, TPL treatment significantly inhibited the expression of GRP78 protein in CNE2 and CNE2-SR cells. These results suggest that TPL may serve as a potential radiosensitizer agent for NPC treatment.