Related Experiment Video
Updated: Aug 14, 2026
Multi-photon Imaging of Tumor Cell Invasion in an Orthotopic Mouse Model of Oral Squamous Cell Carcinoma
Published on: July 25, 2011
Antivascular therapy of oral tongue squamous cell carcinoma with PTK787
Yasemin D Yazici1, Seungwon Kim, Samar A Jasser
1Department of Head and Neck Surgery, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Objectives/Hypothesis:
Vascular endothelial growth factor (VEGF) is an important mediator in tumor vascularization, growth, and metastasis. We investigated whether blockade of the VEGF receptor (VEGF-R) signaling pathway by the tyrosine kinase inhibitor PTK787 combined with CPT-11, a semisynthetic camptothecin analogue, can inhibit the tumor growth and angiogenesis of squamous cell carcinoma of the oral tongue in an orthotopic nude mouse model.
Methods:
JMAR human oral squamous cell carcinoma cells were injected into the tongues of nude mice. Seven days later, the mice were randomized to receive a placebo, daily oral PTK787, weekly CPT-11 injection, or PTK787 plus CPT-11. After 4 weeks of treatment, the mice underwent necropsy, and the tongue tumors, cervical lymph nodes, and lungs were removed for immunohistochemical analyses.
Results:
CPT-11, PTK787, and PTK787 plus CPT-11 significantly decreased tumor volumes and prolonged survival. The combination treatment group had the most significant decrease in volume and increase in survival. PTK787 alone or in combination with CPT-11 reduced the phosphorylation of VEGF-R in tumor cells and tumor-associated endothelial cells, was associated with decreased microvessel density, a decreased proliferative index, and an increased apoptotic index. PTK787 alone or the combination therapy resulted in apoptosis of both tumor cells and tumor-associated endothelial cells.
Conclusions:
These results suggest that targeting VEGF-R tyrosine kinase activity can be an effective therapeutic approach in squamous cell carcinoma of the oral tongue.
Insights
Blocking vascular endothelial growth factor receptor (VEGF-R) with PTK787 and CPT-11 significantly reduced oral tongue squamous cell carcinoma growth and improved survival in mice.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Vascular endothelial growth factor (VEGF) plays a critical role in tumor angiogenesis, growth, and metastasis.
- VEGF receptor (VEGF-R) signaling is a key pathway targeted in cancer therapy.
Purpose of the Study:
- To evaluate the efficacy of PTK787, a VEGF-R tyrosine kinase inhibitor, in combination with CPT-11 against oral tongue squamous cell carcinoma.
- To assess the impact of this combination therapy on tumor growth, angiogenesis, and survival in an orthotopic mouse model.
Main Methods:
- Human oral squamous cell carcinoma cells were implanted into the tongues of nude mice.
- Mice received placebo, PTK787, CPT-11, or a combination of PTK787 and CPT-11 for 4 weeks.
- Tumor volumes, survival rates, and immunohistochemical markers of angiogenesis, proliferation, and apoptosis were analyzed.
Main Results:
- All treatment groups showed decreased tumor volumes and prolonged survival compared to placebo.
- The combination of PTK787 and CPT-11 demonstrated the most significant reduction in tumor volume and increase in survival.
- Combination therapy reduced VEGF-R phosphorylation, decreased microvessel density, and lowered proliferation while increasing apoptosis in tumor and endothelial cells.
Conclusions:
- Targeting VEGF-R tyrosine kinase activity with PTK787, particularly in combination with CPT-11, is a promising therapeutic strategy for oral tongue squamous cell carcinoma.
- This approach effectively inhibits tumor growth and angiogenesis by inducing apoptosis in both cancer and endothelial cells.
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