Antiproliferative effects of ionizing radiation, all‐trans‐retinoic acid, and interferon‐α on cultured human squamous cell carcinomas

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Abstract
In the present study we analyzed the antiproliferative effects of irradiation (IR), all‐trans‐retinoic acid (RA), and interferon‐α (IFN‐α) on two established human cell lines of squamous cell carcinoma of the head and neck (cell line HTB43) and of cervical cancer (cell line HTB35). The determination of the radiosensitivity of these cells using the colony formation assay revealed that the Do value, or radiation dose that reduces survival to e−1 of its previous value on the exponential portion of the survival curve, for both cell lines was identical (2 Gy). The surviving fraction at 2 Gy (SF2) could be demonstrated to be approximately 60% for both cell lines. Treatment of these carcinoma cells either with all‐trans‐RA (dose range 1–10 μM) or with IFN‐α (dose range 0.5–500 IU/ml) resulted in a significant inhibition of colony formation. When the cells were treated with a combination of RA and IFN‐α the growth potential was affected in a synergistic manner. Pretreatment of the squamous cell carcinoma cell lines with RA in combination with IFN‐α for 24 hr followed by a single IR dose of 2 Gy led to a significant potentiation of the radiosensitivity in both lines although this effect was much more pronounced in the cervical cancer cells (HTB35). Cytomorphological and cytochemical analyses revealed that the growth inhibitory activity of RA, IFN‐α, and IR may be ascribed in part to the induction of irreversible postmitotic cells with a more normalized state of differentiation. On the basis of these data, experimental strategies could be developed for future treatment concepts employing RA, IFN‐α, and IR for the therapy of squamous cell carcinomas. © Wiley‐Liss, Inc.