VEGF Modulation by Radiation and Temozolomide in Glioblastoma Cells

Article Outline

• Purpose/Objective(s)
• Materials/Methods
• Results
• Conclusions
• Copyright

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Purpose/Objective(s) 

Glioblastoma (GB) is the most aggressive form of brain cancer, accounting for approximately 40% of all primary malignant brain tumors. One of the hallmarks of GB is its high degree of vascularization. It has been shown that GB cells express vascular endothelial growth factor (VEGF) and is associated with poor prognosis. The standard of therapy for GB patients following surgical resection is concurrent radiation with temozolomide (TMZ), followed by 6 cycles of TMZ. Despite optimal treatment with surgery, radiotherapy, and chemotherapy, the prognosis for these patients remain poor. Radiation has been shown to induce VEGF secretion from glioma cells. The VEGF response of glioma cells to combined RT/TMZ has not been evaluated. This study evaluates the expression of VEGF in GBM cell line U87MG.

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Materials/Methods 

The U87MG cell line was irradiated using Cs-137 sealed source. Cells were grown in 1% FCS media, DMSO, or TMZ media. Conditioned media was harvested and VEGF level was measured using ELISA in the following conditions: by the administration of RT, TMZ, and concurrent RT/TMZ.

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Results 

The U87MG cell line irradiated with 5, 10, 15, and 20 Gy increased VEGF secretion by 1.87, 1.90, 1.57, and 3.15-fold above baseline of no radiation in 48 hours; and 1.82, 1.95, 2.54, and 2.86-fold above baseline of no radiation in 72 hours. The U87 cell line was then treated with DMSO or TMZ in DMSO media and irradiated to 0, 10, and 20 Gy. We showed that addition of TMZ increased VEGF secretion by 1.16-fold compared with no radiation. When the U87 cells were irradiated to 10 Gy, addition of TMZ decreased VEGF secretion by 0.82-fold. Interestingly, when U87 cells were irradiated to 20 Gy, addition of TMZ increased VEGF secretion by 1.43-fold.

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Conclusions 

These data suggest that VEGF secretion in response to radiation and TMZ, the standard of treatment for GB following surgical resection, act in a dose and time-dependent manner. Additional experiments need to be done to confirm these findings. The VEGF modulation opens a broader range of therapeutic possibilities. It is logical that therapies aimed at targeting the VEGF secretion may potentiate the effect of chemoradiation therapy in GB.