Eicosanoids and Radiotherapy in Human and Animal Tumors
Since eicosanoids may influence tumor growth and spread and radiotherapy can increase tissue prostaglandins, it is important to investigate relationships between prostaglandins and radiotherapy in cancer. Our studies in mice with NC carcinoma show that local radiotherapy reduced tumor size and tumors were even smaller when the prostaglandin synthesis inhibitor flurbiprofen was also given. However, we do not know if this reduction was merely due to removal of radiotherapy-induced inflammation. It is of interest to note that prostaglandin synthesis inhibitors increased the response to chemotherapy and the accumulation of methotrexate in malignant cells.
Since prostaglandins can protect certain tissues such as the gastrointestinal mucosa from damage, we determined whether indomethacin affected the viability of normal and malignant cells exposed to 3 Gy X rays. Indomethacin (0.1 or 1 αg/ml) did not alter the viability of epithelial cells from human normal embryonic intestine or their injury by radiotherapy. Indomethacin alone reduced the viability of rat hepatic tumor cells, and this added to the effect of radiotherapy. In neither case did indomethacin alter the response to radiotherapy, and these results argue against “cytoprotection” by prostaglandins.
Studies in breast cancer patients showed primary tumor prostagandin-like material (PG-LM) to correlate with early death. Yields of tumor PG-LM from patients with head and neck cancer (whose tumors were irradiated prior to excision) correlate with the amount of necrosis, inflammation, and fibrosis but not with survival. Plasma PG-LM was measured before and after synchronous radiotherapy and chemotherapy, and both the amount of mucositis and the treatment correlated with the plasma measurements, but this was despite the intake of nonsteroidal anti-inflammatory drugs. The clinical implications of the tumor prostaglandin measurements are not clear. We need to know the influence of prostaglandin synthesis on the response to radiotherapy, and the ability of indomethacin to increase the response to methotrexate is potentially of great importance.
KeywordsCytotoxic Drug Human Intestinal Cell Toad Bladder Arachidonate Metabolite Uninvolved Lymph Node
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