Association of docetaxel/paclitaxel with irradiation in ovarian carcinoma cell lines in bidimensional (sulforhodamine B assay) and tridimensional (spheroids) cultures.
The association of taxoid derivatives (paclitaxel and docetaxel) with irradiation was evaluated in ovarian carcinoma cell lines (A2780 and CAVEOC-2) using the multicellular tumor spheroids (MTS) tridimensional model and compared to the conventional bidimensional model. The radiosensitivity parameters were the surviving fraction at 2 Gy, and alpha calculated using the linear-quadratic model for monolayer culture, the residual/control volume ratios at 2 Gy (RSV2) and doses inducing 50% decrease in MTS number (SCD50) calculated for spheroids. In A2780 monolayer culture, the combination was synergistic for paclitaxel and additive for docetaxel. In spheroids, both compounds induced a decrease in RSV2 and SCD50 in the two cell lines, and their combination with radiation was additive. Therefore, the radiosensitizing effect of taxoid derivatives was not constant in ovarian cell lines. The different results achieved in monolayer culture and in spheroids may suggest higher drug incorporation and fixation through the multiple cell layers of the spheroids than in monolayers.
Laboratoire de Recherche en Oncologie, Centre Alexis Vautrin, Vandoeuvre-les-Nancy Cedex, France.
G
G
Griffon-Etienne
J L
JL
Merlin
C
C
Marchal
D000230:Adenocarcinoma / Q000628:therapy*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D003131:Combined Modality Therapy; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000628:therapy*; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology*; D043823:Taxoids; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel