Radiation sensitivity of human squamous cell carcinoma cells in vitro is modulated by all-trans and 13-cis-retinoic acid in combination with interferon-α

Purpose: Retinoids and interferon-alpha (IFN-alpha) have been shown to exert antiproliferative and radiosensitizing effects. The present study was designed to determine differential effects of retinoids in combination with IFN-alpha on radiation toxicity of 5 human squamous cell carcinoma (SCC) cell lines. Methods and Materials: Using clonogenic assays, the effects of all-trans (ATRA), 13-cis-retinoic acid (13cRA), and IFN-alpha On radiation toxicity were analyzed. Basal mRNA expression of the cytoplasmic retinoic acid binding protein, CRABP I, was determined in retinoid-sensitive and -insensitive cell lines by reverse transcriptase/ polymerase chain reaction (RT-PCR). Results: Treatment with ATRA, 13cRA, or IFN-alpha resulted in a cell line-specific inhibition of clonogenic survival. A comparison of retinoid-sensitive and insensitive cells revealed that retinoid sensitivity seems to be dependent on the basal expression level of CRABP I. ATRA, 13cRA, and IFN-alpha alone or in combination altered radiation sensitivity by affecting predominantly the alpha-component of the linear-quadratic dose-response curve. Likewise, depending upon the treatment condition the surviving fraction at 2 Gy (SF2) was decreased cell line-specifically. Combined treatment with ATRA or 13cRA and IFN-alpha markedly enhanced radiation cytotoxicity. Conclusion: These in vitro data indicate that the combined treatment with retinoids, IFN-alpha, and ionizing radiation could be beneficial for patients presenting with SCC. (C) 1999 Elsevier Science Inc.