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.


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.
Bläse
M
M
Department of Radiotherapy, Eberhard-Karls-University Tübingen, Germany.
Zaruba
M M
MM
Santo-Hoeltje
L
L
Bamberg
M
M
Hoffmann
W
W
Rodemann
H P
HP
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D002470:Cell Survival; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003470:Culture Media; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004338:Drug Combinations; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D015474:Isotretinoin / Q000008:administration & dosage / Q000627:therapeutic use*; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D003470:Culture Media; D004338:Drug Combinations; D016898:Interferon-alpha; D011838:Radiation-Sensitizing Agents; D015474:Isotretinoin