title: Triptolide inhibits cell growth and GRP78 protein expression but induces cell apoptosis in original and radioresistant NPC cells.
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 IC50 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.
authors.affiliation: Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China.
authors.forename: Chengmin
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Histology and Embryology, Xiangya School of Medicine, Central South University, Changsha, Hunan Province 410008, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China.
authors.forename: Wuwu
authors.initials: W
authors.lastname: Lv
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Lai
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China.
authors.forename: Zhikang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Long
authors.affiliation: Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China.
authors.forename: Xueping
authors.initials: X
authors.lastname: Feng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000188:drug therapy*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D004224:Diterpenes / Q000494:pharmacology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D004852:Epoxy Compounds / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy*; D009368:Neoplasm Transplantation; D010616:Phenanthrenes / Q000494:pharmacology*; D011836:Radiation Tolerance
chemical_list: D004224:Diterpenes; D000091342:Endoplasmic Reticulum Chaperone BiP; D004852:Epoxy Compounds; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D010616:Phenanthrenes; C001899:triptolide
keywords: CNE2; GRP78; nasopharyngeal carcinoma; radioresistance; triptolide