Radiation-sensitizing effect of a low concentration of docetaxel on human esophageal squamous cell carcinoma cell lines

Proc Amer Assoc Cancer Res, Volume 47, 2006 4406 Background: While 5-FU/CDDP is the standard regimen used for chemoradiotherapy of esophageal cancer, there are still many unclear aspects about the combined effect of the novel anticancer agent docetaxel and radiation. Purpose: We investigated the radiation-sensitizing effect of docetaxel on human esophageal squamous cell carcinoma cell lines, in which the combined effect of the two treatment modalities has been shown to vary with the contact time. Materials and Methods: We exposed human esophageal squamous cell carcinoma cell lines TE2, TE3 and A431 to docetaxel for 3 hours each, and determined the maximum concentration of the drug at which no cytocidal effect was observed, based the on survival curves and the colony formation assay. The chemo-radiation group was exposed to docetaxel before, during, or after the irradiation, and the cytocidal effect according to the radiation dose was compared between the chemo-radiation group and the irradiation-alone group by Mann-Whitney’s U-test. In addition, nuclear DNA was measured by flow cytometry before and after exposure of each of the cell lines to low-concentration docetaxel, and the proportions of cells in each phase of the cell cycle were calculated. Results: The IC50 values (M) in the docetaxel -alone groups were as follows, in the order of the highest to the lowest sensitivity: A431 cells ; 8.4×10−10, TE3 cells ; 2.8×10−9 , TE2 cells ; 3.2×10−9 . By contrast, in the groups exposed to radiation alone, the D0 (Gy) values were: TE2 cells ; 0.7, TE3 cells ; 1.1, A431 cells ; 1.9 with a reverse order of sensitivity of the three cell lines. In the groups in which radiation and docetaxel were used in combination, a radiation-sensitizing effect of the drug was observed in all the three cell lines when irradiation was conducted after the exposure to docetaxel (p<0.05). Measurement of changes in the proportions of cells in the various phases of the cell cycle by flow cytometry immediately after exposure to low-concentration docetaxel showed an increase in the G2/M cell fraction for all the three cell lines. Conclusion: Docetaxel had a radiation-sensitizing effect on esophageal squamous cell carcinoma cell lines, a finding which is expected to be valuable in chemoradiotherapy against esophageal cancer.