13-cis retinoic acid in combination with interferon-alpha enhances radiation sensitivity of human squamous cell carcinoma cells of the oral cavity.

Background: Preclinical and clinical trials demonstrated the antiproliferative and chemopreventive potential of 13-cis retinoic acid in combination with interferon-alpha. The present study was designed to determine the radiosensitizing potential of both drugs after single and combined treatment of human squamous-cell carcinoma cells of the oral cavity in vitro.
Material and Methods: The study was performed using the human squamous-cell carcinoma cell line SCC4, which was originally established from a tumor of the oral cavity. Based on clonogenic assays, the inhibition of clonogenic activity and radiosensitizing potential of 13-cis retinoic acid and interferon-alpha after single or combined treatment without and with subsequent irradiation was determined.
Results: 13-cis retinoic acid (10 microM) and interferon-alpha (50 IU/ml) showed significant inhibition of clonogenic activity after single treatment. A combined treatment protocol resulted at least in a highly significant additive inhibition of clonogenicity. Treatment with both drugs (5 microM 13-cis retinoic acid, 25 IU/ml IFN-alpha) prior and post irradiation of the cells resulted in a pronounced enhancement of radiation toxicity resulting in significantly decreased SF2- and alpha-values. Combined treatment with both drugs was significantly more effective than single drug treatment.
Conclusions: The data presented indicate that pre- and post-irradiation treatment with 13-cis retinoic acid and interferon-alpha significantly enhance the radiosensitivity of human squamous-cell carcinoma cells, SCC4, in vitro. Therefore, they support the initiation of clinical trials to test the radio-oncological value of such a treatment regime for squamous-cell carcinomas.