title: A novel bioluminescence orthotopic mouse model for advanced lung cancer.
abstract: Lung cancer is the leading cause of cancer-related death in the United States despite recent advances in our understanding of this challenging disease. An animal model for high-throughput screening of therapeutic agents for advanced lung cancer could help promote the development of more successful treatment interventions. To develop our orthotopic lung cancer model, luciferase-expressing A549 cancer cells were injected into the mediastinum of athymic nude mice. To determine whether the model would allow easy monitoring of response to therapeutic interventions, tumors were treated with 30 mg/kg Paclitaxel or were irradiated with 5 fractions of 2 Gy, and tumor burden was monitored using bioluminescence imaging. Evidence of radiation-induced lung injury was assessed using immunohistochemical staining for phospho-Smad2/3 and cleaved caspase-3. We found that tumor implantation recapitulated advanced human lung cancer as evidenced by tumor establishment and proliferation within the mediastinum. The tumor responded to Paclitaxel or radiation as shown by decreased tumor bioluminescence and improved overall survival. Immunohistochemistry revealed increased phospho-Smad2/3 and cleaved caspase-3 in irradiated lungs, consistent with radiation-induced lung injury. This orthotopic lung cancer model may help provide a method to assess therapeutic interventions in a preclinical setting that recapitulates locally advanced lung cancer.
authors.affiliation: Department of Radiation Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37232, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Artour
authors.initials: A
authors.lastname: Torossian
authors.forename: Wenyan
authors.initials: W
authors.lastname: Li
authors.forename: Stephen
authors.initials: S
authors.lastname: Schleicher
authors.forename: Kathy
authors.initials: K
authors.lastname: Niu
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Giacalone
authors.forename: Sung June
authors.initials: SJ
authors.lastname: Kim
authors.forename: Heidi
authors.initials: H
authors.lastname: Chen
authors.forename: Adriana
authors.initials: A
authors.lastname: Gonzalez
authors.forename: Luigi
authors.initials: L
authors.lastname: Moretti
authors.forename: Bo
authors.initials: B
authors.lastname: Lu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007267:Injections; D008156:Luciferases / Q000235:genetics; D008163:Luminescent Measurements; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy; D051379:Mice; D057054:Molecular Imaging; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use; D011833:Radiation Injuries, Experimental / Q000378:metabolism; D014162:Transfection
chemical_list: D008156:Luciferases; D017239:Paclitaxel