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.

Image-guided radiotherapy platform using single nodule conditional lung cancer mouse models

“…Amongst the associated limitations with these models are: ectopic implantation of cancerous cells, lack of a functional immune system, and altered tumour vasculature. Two recent studies report on model improvements by orthotopic transplantation of human lung cancer cells for studying radiation biology in vivo 5 , 6 .…”

Endotoxin induces proliferation of NSCLC in vitro and in vivo: role of COX-2 and EGFR activation

“…As the currently described short-time tumor-promoting effects of endotoxin detected in vitro and in the subcutaneous tumor model might not reflect the physiological situation exactly, the effects of endotoxin and the potential mechanisms (i.e., TLR4, EGFR, COX-2 activation,) need to be validated in orthotopic lung cancer models, for example, in recently described in situ models using bioluminescence [47, 48]. …”

Liposome as nanocarrier: Site targeted delivery in lung cancer

“…Gaspar et al [94] studied that a valuable remedy is attained by combining the gasp treatment and drug targeting methods (Tf)-conjugated PEG liposomes encumbered with DOX were given by intracorporeal nebulizing tube to lung cancer of rat model [95]. Various DOX products and dosage (0.2 and 0.4 mg/kg) were experienced for their effect on cancer progression.…”