title: Celecoxib-erlotinib combination treatment enhances radiosensitivity in A549 human lung cancer cell.
abstract: BACKGROUND
  Radiosensitivity by blocking the epidermal growth factor receptor and cyclooxygenase-2 pathways with erlotinib and celecoxib in A549 human lung cancer cell was investigated.
  
  
  METHODS
  MTT assays were used to detect the antitumor effects of erlotinib and celecoxib in A549 cells. Colony formation assays were used to evaluate the antitumor effects. Flow cytometry analysis was used to assess the cell cycle and cell apoptosis, and western blotting analysis was performed to evaluate the expression of AKT and phosphorylated AKT.
  
  
  RESULTS
  Either erlotinib or celecoxib inhibited the A549 cell proliferation in a dose-dependent manner. Combining Erlotinib or celecoxib with radiation can suppress the cell colony formation and the Dq, D0, SF2 of the combining erlotinib or celecoxib with radiation was lower than in the combinations either erlotinib or celecoxib with radiation (t= 6.62, P< 0.05). The SER of radiation with celecoxib or erlotinib and celecoxib and erlotinib were 1.299, 1.503 and 2.217, respectively. The Flow cytometry analysis results showed that either celecoxib or erlotinib could induce G0/G1 arrest, and reduction of S phase cell proportion, especially when combinations erlotinib-celecoxib with radiation. Either celecoxib or erlotinib could enhance radiation-induced apoptosis, especially significant when combinations erlotinib-celecoxib with radiation. Moreover, radiation can promote the expression of pAKT, and the pAKT was remarkably lowest in the combinations erlotinib-celecoxib with radiation group (t= 4.89, P< 0.05).
  
  
  CONCLUSIONS
  Blocking both EGFR- and COX-2-related pathways could enhance the antitumor effect of radiation. The underlying mechanisms including the enhancement of apoptosis and radiation-induced G0/G1 arrest, possibly via inhibiting the PI3K/AKT signaling pathway.
authors.affiliation: Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China.|Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin 300060, China.|Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China.|Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin 300060, China.|Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.
authors.forename: Ning-Bo
authors.initials: NB
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China.|Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin 300060, China.|Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.
authors.forename: Hong-Qing
authors.initials: HQ
authors.lastname: Zhuang
authors.affiliation: Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China.|Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin 300060, China.|Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.
authors.forename: Lun-Jun
authors.initials: LJ
authors.lastname: Zhao
authors.affiliation: Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China.|Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin 300060, China.|Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Yuan
authors.affiliation: Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China.|Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin 300060, China.|Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000072283:A549 Cells; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D000068579:Celecoxib / Q000008:administration & dosage*; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D051546:Cyclooxygenase 2 / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011836:Radiation Tolerance / Q000187:drug effects
chemical_list: D000081082:Phosphoinositide-3 Kinase Inhibitors; D000069347:Erlotinib Hydrochloride; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D051058:Oncogene Protein v-akt; D000068579:Celecoxib
keywords: Celecoxib; erlotinib; lung adenocarcinoma; radiosensitizing