title: Resveratrol enhances the radiosensitivity of nasopharyngeal carcinoma cells by downregulating E2F1.
abstract: Identification of safe, effective radiosensitizing agents is urgently needed to improve the outcome of radiotherapy in nasopharyngeal cancer (NPC). In this study, we assessed the ability of the polyphenol resveratrol to act as a radiosensitizer in vitro and in vivo. CNE-1 cells were treated with 50 µM resveratrol for 24 h, then irradiated. E2F transcription factor 1 (E2F1) was stably knocked down and overexpressed using lentiviruses. A xenograft model of NPC was established in nude mice using CNE-1 cells. Compared to control DMSO‑treated CNE-1 cells, resveratrol inhibited colony-forming ability and induced G1 phase cell cycle arrest. Radiation survival curves confirmed resveratrol significantly sensitized CNE-1 cells, and resveratrol in combination with 2 Gy irradiation synergistically increased apoptosis. Immunoblotting showed resveratrol dose- and time-dependently downregulated E2F1 and phospho-AKT (p-AKT). Knockdown of E2F1 significantly increased radiosensitivity and downregulated p-AKT; overexpression of E2F1 reversed resveratrol-induced radiosensitivity and upregulated p-AKT. In vivo, 50 mg/kg/day resveratrol and 4 Gy irradiation led to significantly lower tumor volume and tumor weight compared to resveratrol or irradiation alone. Our findings show that resveratrol increases the radiosensitivity of NPC cells by downregulating E2F1 and inhibiting p-AKT, and therefore has potential as a radiosensitizer for NPC.
authors.affiliation: Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Medical Instruments, Guangdong Food and Drug Vocational College, Guangzhou, Guangdong 510520, P.R. China.
authors.forename: Xianli
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Wenyin
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Pathology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Biaoyan
authors.initials: B
authors.lastname: Du
authors.affiliation: Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Xiao
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D059248:Chemoradiotherapy; D050687:E2F1 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D011838:Radiation-Sensitizing Agents; D013267:Stilbenes; D051057:Proto-Oncogene Proteins c-akt; D000077185:Resveratrol