Introduction: Lung cancer leads in mortality among all types of cancer in US and Non-small cell lung cancer (NSCLC) is the major type of lung cancer. Mice models of lung cancer based on subcutaneous or orthotopic inoculation of cancer cell suspension do not adequately mimic the progression of lung cancer in clinic. Methods: A549-iRFP cells (human NSCLC adenocarcinoma) were cultured to form multicellular spheroids (MCS), which were then inoculated intrapulmonarily into male athymic nude mice. The xenograft cancer development was monitored by in vivo fluorescent imaging and validated by open-chest anatomy, ex vivo fluorescent imaging, and histological studies. Results: The newly developed orthotopic xenograft model of lung cancer simulated all four clinical stages of NSCLC progression over one month: Stage 1) localized tumor at the inoculation site, Stage 2) multiple tumor nodules or larger tumor nodule on the same side of the lung, Stage 3) cancer growth on heart surface, and Stage 4) metastatic cancer on both sides of the lung. The model yielded high rates of postoperative survival (100%) and parenchymal tumor establishment (88.9%). The roughness of the inoculated MCS associated negatively with the time needed to develop metastatic cancer (p = .0299). Discussion: This new orthotopic xenograft model of NSCLC would facilitate the development of medications to treat lung cancer.
|Original language||English (US)|
|Journal||Journal of Pharmacological and Toxicological Methods|
|State||Published - Jul 1 2020|
Bibliographical noteFunding Information:
This work was partially supported by University of the Pacific Seed Grant. We thank Prof. William Chan for access to the infrared fluorescent imaging system and Prof. John Livesey for access to the microplate reader and for suggestion on the manuscript.
- Animal model
- Cancer progression
- Multicellular spheroid
- Non-small cell lung cancer