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


CONCLUSIONS
These in vitro data indicate that the combined treatment with retinoids, IFN-alpha, and ionizing radiation could be beneficial for patients presenting with SCC.
Hoffmann
W
W
Department of Radiooncology, Eberhard-Karls-University Tübingen, Germany.
Bläse
M A
MA
Santo-Hoeltje
L
L
Herskind
C
C
Bamberg
M
M
Rodemann
H P
HP
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D015474:Isotretinoin / Q000008:administration & dosage; D009363:Neoplasm Proteins / Q000378:metabolism; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D014212:Tretinoin / Q000008:administration & dosage; D014407:Tumor Cells, Cultured
D016898:Interferon-alpha; D009363:Neoplasm Proteins; D011838:Radiation-Sensitizing Agents; D018168:Receptors, Retinoic Acid; C082927:retinoic acid binding protein I, cellular; D014212:Tretinoin; D015474:Isotretinoin