Tumor necrosis factor-alpha suppresses the regrowth of fractionated irradiated endothelial cells in vitro.

Abstract

Cytokines from two sources may affect endothelial cells (ECs) in tumor therapy: endogenously from cells in tumors and exogenously from therapeutic applications. These cytokines could modulate the influence of other therapy on tumor ECs. We use the colorimetric MTT method to assess the growth of irradiated ECs isolated from bovine pulmonary artery (CPAEC) and human umbilical cord vein (HUVEC) treated by cytokines. CPAECs given a single radiation dose of 2.5 to 15 Gy showed a small reduction in viable cells 2 to 3 days post-treatment. Neither tumor necrosis factor-alpha (TNF), interleukin-1 alpha (IL-1), nor interferon-gamma (INF) altered the growth of CPAECs treated by single radiation doses. HUVECs irradiated by a single dose of 12 Gy showed continuous reduction in viable cell numbers while those treated by 3 fractions of 4 Gy in 3 days or 6 fractions of 2 Gy in 3 days began to regrow 7 to 8 days after irradiation. Addition of TNF during the fractionated irradiation period limits the regrowth of HUVECs. Addition of IL-1 does not have the same effect. We have also tested the combined effect of another EC active agent flavone acetic acid (FAA), which has also been shown to stimulate the expression of TNF, with radiation, FAA (200 micrograms/ml) has a greater inhibitory effect on the growth and regrowth of fractionatedly irradiated HUVECs than TNF. These data suggest that TNF or FAA should be explored along with radiotherapy for their anti-tumor effect.