Key result
Carbon-ion irradiation of lung carcinoma cells significantly induced VEGF mRNA expression with a maximum induction of 2.81-fold and increased protein levels in a dose-dependent manner.
Why the study?
Does carbon-ion irradiation induce VEGF expression in lung carcinoma cells?
Does carbon-ion irradiation induce VEGF expression in lung carcinoma cells?
Effect estimate: 2.81-fold maximum induction
Carbon-ion irradiation induces dose-dependent VEGF mRNA and protein expression in lung carcinoma cells, mediated by Src tyrosine kinase and protein kinase C.
Does not support practice changes in carbon-ion lung cancer therapy; hypothesis-generating for VEGF-targeted strategies pending further validation.
PURPOSE: To investigate the induction by carbon- ion irradiation of vascular endothelial growth factor (VEGF) mRNA and protein. MATERIALS AND METHODS: RERF-LC-AI lung squamous carcinoma cells were irradiated with carbon ions of either 13.3, 50 or 90keV/microm. Colony formation was used to determine cell survival. VEGF mRNA and protein of the irradiated cells were quantified by Northern blot analysis and ELISA assay, respectively. Genistein, Src tyrosine kinase inhibitor and H7, protein kinase C inhibitor, were used to inhibit VEGF mRNA expression. RESULTS: The relative biological effectiveness (RBE) of carbon ions (13.3, 50 and 90keV/microm) was 1.10, 1.97 and 2.30, respectively, in terms of D10 values. Single doses of 15 Gy with either X-rays or carbon ions significantly induced VEGF mRNA expression at 16-24h after irradiation with a maximum induction of 2.81-fold. A significant increase was also observed in VEGF protein levels, detected in culture supernatant 24h after irradiation with 50 and 90keV/microm carbon ions. Neither mRNA nor protein induction showed a dependence on LET. The induction of VEGF mRNA by carbon-ion irradiation was completely inhibited by pretreating cells with genistein and H7, indicating that Src tyrosine kinase and protein kinase C on cell surface membranes is involved in the induction. CONCLUSION: Irradiation of lung carcinoma cells with carbon ions induced VEGF mRNA expression and increased protein levels. The induction was dose-dependent. Radiation-induced DNA damage and/or its repair may not be a prerequisite for the induction of VEGF mRNA.
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K. Nojima S. Ando (2000) studied Lung squamous carcinoma (RERF-LC-AI cells). Carbon-ion irradiation vs. X-rays was evaluated on VEGF mRNA and protein expression (2.81-fold maximum induction). Carbon-ion irradiation of lung carcinoma cells significantly induced VEGF mRNA expression with a maximum induction of 2.81-fold and increased protein levels in a dose-dependent manner.