This study was performed to evaluate the radiosensitizing effect of combined administration of 13-cis-retinoic acid (cRA) and interferon-alpha-2a (INF) in normal cervical keratinocyte and cervical cancer cell lines.

cRA, INF and radiotherapy was applied to cervical cancer cell lines (HT-3 and HeLa cells) to obtain optimum dose 20% cytotoxicity in MTT assay from each treatment. The dose was determined as 1.8 Gy for radiation, 10uM for cRA, and 1,000 U/ml for INF. Primary cultured cervical keratinocyte (PCCK), HT-3 and HeLa cells were treated with cRA and INF alone or in combination and compared with untreated control cells. Finally, radiotherapy was added to the cRA and INF treatment.

The treatment of cRA and INF-alpha reduced significantly the mean number of colony of HT-3 cells from 250 (SD, 19) to 143 (SD, 32). In contrast, PCCK and HeLa cells exhibited less than 15% reduction of colony formation with the treatment of cRA and INF-alpha. Irradiation of HT-3 cells reduced the colony formation significantly (from 63.6% to 18.4%, p=0.002) after treatment of cRA and INF-alpha. However, PCCK and HeLa cells showed 13.2% (from 70.0 to 56.8%, p=0.807) and 8.4% (from 60.8% to 52.4%, p=0.816) reduction of their colonies respectively.

These results suggested that the treatment of cRA and INF-alpha showed significant radiosensitizing effect in HPV-negative HT-3 cells but not in the normal cervical cells or HPV-positive HeLa cervical cancer cells.