A novel bioluminescence orthotopic mouse model for advanced lung cancer

Bo Li, Artour Torossian, Wenyan Li, Stephen Schleicher, Kathy Niu, Nicholas J. Giacalone, Sung June Kim, Heidi Chen, Adriana Gonzalez, Luigi Moretti, Bo Lu

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)486-493
Number of pages8
JournalRadiation Research
Volume176
Issue number4
DOIs
StatePublished - Oct 1 2011

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

Fingerprint Dive into the research topics of 'A novel bioluminescence orthotopic mouse model for advanced lung cancer'. Together they form a unique fingerprint.

  • Cite this

    Li, B., Torossian, A., Li, W., Schleicher, S., Niu, K., Giacalone, N. J., Kim, S. J., Chen, H., Gonzalez, A., Moretti, L., & Lu, B. (2011). A novel bioluminescence orthotopic mouse model for advanced lung cancer. Radiation Research, 176(4), 486-493. https://doi.org/10.1667/RR2565.1