title: Darbufelone, a novel anti-inflammatory drug, induces growth inhibition of lung cancer cells both in vitro and in vivo.
abstract: OBJECTIVE
  Inflammation plays a crucial role in the development of lung cancer. Accumulated studies have proved that non-steroidal anti-inflammatory drugs (NSAIDs) which block inflammation by their actions on arachidonic acid (AA) metabolism have a potential role in cancer chemotherapy and chemoprevention. The aim of our study was to investigate whether darbufelone, a novel anti-inflammatory drug, has anticancer effects in lung cancer.
  
  
  METHODS
  Human non-small cell lung cancer cell lines were treated with darbufelone at various doses and time points for analysis of cell viability, cell cycle, and apoptosis in vitro. The in vivo effect of darbufelone was assessed in Lewis lung carcinoma mice model.
  
  
  RESULTS
  Darbufelone inhibited the proliferation of non-small cell lung cancer cell lines in a dose-dependent manner, and induced cell cycle arrest at G0/G1 phase through up-regulation of p27 expression. Treatment with darbufelone also induced apoptosis by activating caspase-3 and caspase-8. Lewis lung carcinoma growth was also significantly inhibited by darbufelone treatment at daily dose of 80 mg/kg.
  
  
  CONCLUSIONS
  Taken together, these studies suggested that darbufelone, an anti-inflammation drug, might represent a novel therapeutic approach for lung cancer treatment.
authors.affiliation: Department of Pharmacology, China Pharmaceutical University, 24 Tong Jia Xiang, 210009, Nanjing, People's Republic of China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Ye
authors.forename: Wu
authors.initials: W
authors.lastname: Zhou
authors.forename: Yongqi
authors.initials: Y
authors.lastname: Li
authors.forename: Yihua
authors.initials: Y
authors.lastname: Sun
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Ji
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Lai
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000970:Antineoplastic Agents; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D049109:Cell Proliferation / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053778:Thiazolidines / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D053778:Thiazolidines; D050760:Cyclin-Dependent Kinase Inhibitor p27; C109268:darbufelone; D053148:Caspase 3; D053181:Caspase 8