本郷 淳司

The in vitro radiosensitizing effects of docetaxel have been reported, but the DNA damage caused by the irradiation after docetaxel exposure has not been investigated. In this study, the authors attempted to evaluate the radiosensitizing effects in terms of cell survival and DNA single-strand breaks in a human ovarian adenocarcinoma cell line (known as line BG-1) and a human cervical squamous cell carcinoma cell line (known as line SiHa). The cell lines were exposed to various concentrations of docetaxel (from 2.27 x 10(-3) to 2.27 microg/ml) to investigate the cytocidal effects by colony-formation assay. DNA single-strand breaks after exposure to 2.27 microg/ml of docetaxel for 30 min or 100 min were measured by the alkaline-elution assay. The remarkable cytotoxicity of docetaxel followed by irradiation was observed when concentrations were greater than 2.27 x 10(-2) microg/ml in both cell lines. The combination of docetaxel and irradiation appears to be supraadditive. The DNA single-strand breaks induced by the irradiation were enhanced in both cell lines (BG-1; P < 0.01, SiHa; P < 0.05). The synergistic cytocidal effect cannot be explained quantitatively only by the single-strand breaks.

The insulin-like growth factor I receptor (IGF-IR) is exceptionally overexpressed in many cervicalcancer-derived cell lines. It is postulated that a decrease of p53 protein levels due to human papillomavirus (HPV) infection may contribute to the up-regulation of IGF-IR expression in cervical cancer cells because transcription of IGF-IR is strictly down-regulated by p53. To evaluate this fact in clinical cervical cancer specimens, we checked the expression levels and activated status of IGF-IR by immunohistochemistry. Formalin-fixed and paraffin-embedded specimens obtained by conization or hysterectomy were stained with anti-IGF-IR and with an antibody recognizing phosphorylated tyrosine at its c-terminus. The expression levels of IGF-IR were significantly high in cervical intraepithelial neoplasia (CIN) III and invasive cancer specimens. Phosphorylation of IGF-IR was promoted in all CIN and invasive cancer specimens, and its intensity was related to the promotion of lesions. Interestingly, IGF-IR overexpression was missing in the basal layer of CIN I and II lesions, whereas it was evenly distributed in CIN III and invasive cancer lesions. This IGF-IR overexpression pattern may be utilized in the diagnosis of HPV infection status in CIN lesions.