Paclitaxel inhibits radiation induced VEGF secretion and enhances radiosensitizing effects in human colon cancer cell HT29

This study investigated that 5-fluorouracil (5-FU) or Paclitaxel (PXL) pretreatment in clinical doses modifies the radio-enhance effect and angiogenetic molecule on human colon cancer cell line HT29. Cell growth inhibition by each drug at various concentrations followed by radiation was investigated using a WST-8 colorimetric assay. To investigate the mechanism of radioenhancement, flow cytometry was conducted to define the cell cycle distributions. Furthermore, the alterations in expression of an angiogenesis factorvascular endothelial growth factor, (VEGF) induced by each drug were investigated. Each drug inhibited cell growth and acted as radiosensitizer in a dose- and time-dependent manner. Cytotoxic concentrations of PXL that cause accumulation of cells in the G2/M phase have strong radio-enhancing effects. In contrast, 5-FU did not affect cell cycle distributions. The maximum non-cytotoxic concentrations of 5-FU and PXL were 0.1μM and 0.01μM, respectively. Radiosensitizing effect at non-cytotoxic dose of PXL was significantly greater than that of 5-FU. The gene expression and protein of VEGF induced by radiation was suppressed by PXL treatment, but this phenomenon was not recognized in 5-FU treatment. PXL pretreatment had the potential to act as radiosensitizer even at non-cytotoxic dose. Furthermore, Radiation induced VEGF were significantly down-regulated by PXL pretreatment. These data indicated that PXL might have a high potential for clinical use in neoadjuvant chemoradiotherapy and for inhibition of radiation induced VEGF production in colorectal cancer.