Interaction of ionizing radiation with paclitaxel (Taxol) and docetaxel (Taxotere) in HeLa and SQ20B cells.
Altered gamma-ray response by brief (1 h), concomitant exposure to paclitaxel (Taxol) or docetaxel (Taxotere) was investigated in growing HeLa and SQ20B human tumor cells in vitro. For both cell lines, both taxoids were able to reduce or enhance radiation cell killing, depending on the drug concentration. Large reduction of radiosensitivity (up to 3.3-fold reduction relative to radiation alone) was observed in HeLa cells over a wide range of drug concentrations, extending to 1.5- (paclitaxel) or 3.3- fold (docetaxel) the IC50s determined for drug alone. This antagonistic effect was also observed with SQ20B cells. It disappeared for drug concentrations exceeding 0.9 (SQ20B), 1.6 (HeLa; paclitaxel), and 3.4 (HeLa; docetaxel) IC50 equivalents, above which a drug dose-dependent, supra-additive radiation-drug interaction was observed. Reduction of radiation susceptibility in the low-drug dose range also held for mid-G1 synchronized HeLa cells, i.e., in the cell cycle compartment characterized as the most resistant one to docetaxel (C. Hennequin et al., Br. J. Cancer, 71: 1194-1198, 1995). In the case of SQ20B cells, the cytotoxicity of either drug or radiation alone was primarily dependent on the state of growth, with quiescent (G(0)) cells showing increased radiosensitivity and reduced drug toxicity compared to the growing fraction. The effect of taxoids (1-h contact) was finally investigated in sequential treatment as a function of the time elapsed between radiation and exposure to drugs. In HeLa cells, the postirradiation time-dependence of the response to combined treatment was biphasic. The radioprotecting potential of either taxoid disappeared in approximately 1.5 h following radiation. At longer postirradiation delays, radiation-induced redistribution in the cell cycle appeared to be the major determinant of HeLa cell survival, in relation to the differential cell cycle phase specificity of each drug. Pronounced paclitaxel recovery versus increased sensitivity to docetaxel occurred over 8 h after irradiation. SQ20B cells showed monophasic radiation recovery with both drugs over the same time range.
Hennequin
C
C
Unite 350 INSERM, Institut Curie-Biologie, Orsay, France.
Giocanti
N
N
Favaudon
V
V
D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D006367:HeLa Cells; D006801:Humans; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000633:toxicity*; D011838:Radiation-Sensitizing Agents / Q000633:toxicity*; D043823:Taxoids; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000972:Antineoplastic Agents, Phytogenic; D011838:Radiation-Sensitizing Agents; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel