title: Inhibition of autophagy enhances the radiosensitivity of nasopharyngeal carcinoma by reducing Rad51 expression.
abstract: Radiotherapy has long been considered as the mainstay of treatment for nasopharyngeal carcinoma (NPC). However, locoregional recurrence or distant metastasis may occur in some patients due to the radiation resistance of cancer cells. Autophagy plays a vital role in protecting cells against radiation. However, the mechanism of autophagy in radiation therapy remains obscure. In the present study, we demonstrated that suppression of autophagy related 5 (Atg5) aggravated ionizing radiation (IR)-induced DNA damage and apoptosis in human NPC cells without accelerating the cell cycle, whereas regulation of the cell cycle has been widely regarded as the most important determinant of IR sensitivity. Further study showed that inhibition of autophagy suppressed the mRNA expression of Rad51, a key protein of homologous recombination that has been demonstrated to play a critical role in the repair of DNA double-strand breaks induced by radiation. Moreover, suppression of Atg5 had no impact on the radiosensitivity when cells were pre-treated by the Rad51 inhibitor, and the enhanced radiosensitivity by Atg5 suppression was reversed by overexpression of Rad51 in human NPC cells. Our results suggest that inhibition of autophagy enhances the susceptibility of NPC cells to radiation by reducing Rad51 expression. Therefore, Rad51 targeted therapy may be investigated as a potential novel agent for the adjuvant treatment of traditional radiation of NPC.
authors.affiliation: The Fifth Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Mo
authors.affiliation: The Fifth Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, P.R. China.
authors.forename: Yong-Kui
authors.initials: YK
authors.lastname: Lu
authors.affiliation: The Fifth Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, P.R. China.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Xie
authors.affiliation: The Fifth Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Fifth Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, P.R. China.
authors.forename: Wen-Xian
authors.initials: WX
authors.lastname: Zhou
authors.affiliation: The Fifth Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, P.R. China.
authors.forename: Hong-Xue
authors.initials: HX
authors.lastname: Wang
authors.affiliation: The Fifth Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Nong
authors.affiliation: The Fifth Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, P.R. China.
authors.forename: Yu-Xian
authors.initials: YX
authors.lastname: Jia
authors.affiliation: The Fifth Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, P.R. China.
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Tan
authors.affiliation: The Fifth Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: The Fifth Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, P.R. China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Li
authors.affiliation: The Fifth Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, P.R. China.
authors.forename: Bao-Hua
authors.initials: BH
authors.lastname: Luo
mesh_terms: D001343:Autophagy / Q000187:drug effects; D000071187:Autophagy-Related Protein 5; D002277:Carcinoma; D045744:Cell Line, Tumor; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D034741:RNA, Small Interfering / Q000378:metabolism; D051135:Rad51 Recombinase / Q000235:genetics*; D011836:Radiation Tolerance
chemical_list: C502778:ATG5 protein, human; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D004247:DNA; C495153:RAD51 protein, human; D051135:Rad51 Recombinase