Neoadjuvant treatment with docetaxel and the effects of irradiation for human ovarian adenocarcinoma and cervical squamous cell carcinoma in vitro.
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.
Araki
Shinako
S
Department of Obstetrics and Gynecology, Okayama University Medical School, Japan.
Miyagi
Yasunari
Y
Kawanishi
Kunihiro
K
Yamamoto
Junko
J
Hongo
Atsushi
A
Kodama
Junichi
J
Yoshinouchi
Mitsuo
M
Kudo
Takafumi
T
D000230:Adenocarcinoma; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell; D003131:Combined Modality Therapy; D004277:DNA, Single-Stranded / Q000528:radiation effects; D000077143:Docetaxel; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000528:radiation effects; D010051:Ovarian Neoplasms; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D043823:Taxoids; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D002583:Uterine Cervical Neoplasms
D000972:Antineoplastic Agents, Phytogenic; D004277:DNA, Single-Stranded; D011838:Radiation-Sensitizing Agents; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel