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K. Kondo
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-108 - Non-Invasive Assessment of Cisplatin and Erlotinib Efficacy in Lung Cancer by Monitoring an Orthotopic SCID Mouse Model with Computed Tomography (ID 1317)
09:30 - 09:30 | Author(s): K. Kondo
- Abstract
Background:
Orthotopic models are likely to provide more relevant pharmacokinetic and pharmacodynamic information than subcutaneous models. We established an orthotopically implanted SCID mouse model of lung cancer without thoracotomy. This model is simple and reproducible and many transplanted mice can be produced at once. The main disadvantage of the orthotopic model is that tumor size and volume changes are difficult to continuously monitor reproducibly and can only be assessed at necropsy. In this study, we evaluated the usefulness of small-animal computed tomography (CT) to non-invasively and repeatedly monitored the inhibitory effect of cisplatin and erlotinib on lung cancer in an orthotopic SCID mouse model. Our goal was to establish a standard model to evaluate efficacy of novel treatment regimens in lung cancer.
Methods:
We created an orthotopic lung cancer transplantation model in mice. Suspensions of 2.0 × 10[4] cancer cells were injected into the left lung of SCID mice. We tested several non-small cell lung cancer cell lines, A549, FT821 and PC9 cells—only PC9 cells have an epidermal growth factor receptor (EGFR) mutation. We treated mice with cisplatin or erlotinib. When tumor volume had reached 1–3 mm[3], mice were divided into three groups: control, cisplatin and erlotinib. After treatment had begun, tumor volumes were evaluated by CT measurement every 3 days. All mice were sacrificed for histopathological analysis on day 18 after treatment began.
Results:
Mice implanted with A549, FT821 and PC9 cells were treated beginning on day 21, 50 and 35, respectively, after implantation. In mice transplanted with PC9 cells, tumor volume in the cisplatin group measured by CT was lower than in the control group, though not achieving statistical significance. In mice with A549 cells, tumor volume in the cisplatin group was similar to that in the control group. In mice with FT821 cells, tumor volume in the cisplatin group was significantly lower than in the control group. The mice in the cisplatin group showed temporarily decreased body weights. Histopathological analysis on day 18 after treatment showed necrotic lesions in lungs of mice transplanted with PC9 and FT821 cells but not in those with A549 cells. In mice with PC9 cells, which have a deletion of exon 19 in the EGFR gene, tumor volume in the erlotinib group was significantly lower than in the control group. In mice with A549 and FT821 cells, tumor volume in the erlotinib group was similar to that in the control group. There were no body weight changes in the erlotinib group. Histopathological analysis on day 18 after treatment showed necrotic lesions in lungs of mice implanted with PC9 cells but not in those with A549 and FT821 cells.
Conclusion:
This study supports using CT to monitor, non-invasively and repeatedly, tumor progression and therapeutic response of lung cancer in an orthotopic mouse model. This model is more analogous to the clinical condition than subcutaneously transplanted tumor models. Therefore, orthotopic tumor models have potential value as fundamental tools for the design and development of new therapies for cancer treatment.
