title: Association of ribosomal protein S6 kinase 1 with cellular radiosensitivity of non-small lung cancer.
abstract: Ribosomal S6 kinase 1 (S6K1) plays an important role in cell proliferation, protein translation and cell survival. This study investigated the possibility of using S6K1 as a new target in the radiotherapy of non-small cell lung cancer (NSCLC) and its potential mechanism.
  
  
  
  shRNA interference technology was applied to silence the expression of S6K1 in A549 and H460, and clonogenic assay was performed to measure the radiosensitizing effects. DNA repair was monitored by γH2AX foci formation. Cell cycle and apoptosis were measured by flow cytometry assays. Protein expression was analyzed by Western blotting. S6K1 and lentivirus containing programmed cell death 4 (PDCD4), a substrate of S6K1, were co-transfected into cells and radiosensitivity was also detected.
  
  
  
  S6K1 knockdown significantly enhanced the radiosensitivity of NSCLC cells. The notable findings in response to this combined treatment were prolonged delay in radiation-induced DNA DSB repair, robust G2/M checkpoint arrest, increased apoptosis and upregulation of PDCD4. Moreover, PDCD4 knockdown reversed the radiosensitizing effects of S6K1 inhibition in NSCLC.
  
  
  
  S6K1 is a promising tumor-specific target for the enhancement of NSCLC radiosensitivity and its effects may be mediated by increased expression of PDCD4.
authors.affiliation: a Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.affiliation: b Department of Pediatric Surgery , Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Hong
authors.initials: H
authors.lastname: Mei
authors.affiliation: c Critical Care Medicine , The First Affiliated Hospital of Nanchang University , Nanchang , Jiangxi , China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shao
authors.affiliation: a Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: a Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Lin
mesh_terms: D000072283:A549 Cells; D017209:Apoptosis / Q000528:radiation effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000532:radiotherapy*; D011836:Radiation Tolerance; D011879:Radiotherapy Dosage; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D038762:Ribosomal Protein S6 Kinases, 70-kDa; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1
keywords: PDCD4; S6K1; non-small cell lung cancer; radiosensitization