Sensitivity to taxoid derivatives of a newly established human endometrioid ovarian adenocarcinoma radioresistant cell line.

An endometrioid ovarian adenocarcinoma cell line CAVEOC-2 was characterized. Maintained in monolayered culture, CAVEOC-2 cells exhibited a 33-hr doubling time. When xenografted into nude mice, these cells produced fast growing tumors. Colony-forming efficiency in agar was 50%. DNA index was 1.5 and cytogenetic analysis showed a triploid karyotype. CAVEOC-2 cells did not express mdr-1 gene and were chemosensitive to doxorubicin (IC50 = 1.82 +/- 0.76 mumol/l), paclitaxel (IC50 = 3.33 +/- 0.26 nmol/l) and docetaxel (IC50 = 0.68 +/- 0.28 nmol/l), while they showed an intermediate sensitivity to cisplatin (IC50 = 9.40 +/- 1.02 mumol/l). CAVEOC-2 cells seemed highly radioresistant (SF2 = 0.81, alpha = 0.02 Gy-1, beta = 0.025 Gy2, and MID = 4.31 Gy). Activities of glutathione S transferase and gamma-glutamyl transpeptidase were respectively 23.5- and 3.4- fold higher than those of sensitive A2780 cell line. These characteristics make the CAVEOC-2 cells a suitable model for the study of human endometrioid ovarian adenocarcinoma.

Comparison of sulforhodamine B, tetrazolium and clonogenic assays for in vitro radiosensitivity testing in human ovarian cell lines.

The radiation sensitivity of six human ovarian tumor cell lines was evaluated using sulforhodamine B (SRB), tetrazolium (MTT) and clonogenic assays. Radiobiological parameters calculated from a linear quadratic model (SF2, alpha, beta) as well as from a single-hit multitarget model (D(o), Dq, n) and from the area under the dose-response curve (mean inactivation dose; MID) were compared. If the values deduced from MTT experiments were statistically comparable to those obtained from clonogenic assays, significant differences were observed between SRB and the two other assays that concerned the results achieved with the highest radiation doses tested (6-8 Gy), yielding a surviving fraction of approximately 20%. In addition, the intra- and inter-experimental variation of SRB dramatically increased within this range of radiation doses. However, up to 6 Gy, the SRB assay proved to be statistically comparable to MTT and clonogenic assays, and allowed the calculation of SF2, alpha and MID radiobiological parameters.

Radiosensitivity of multicellular tumour spheroids obtained from human ovarian cancers.

The radioresponsiveness of immunologically characterised (KL1, antivimentin and OC125) human ovarian carcinoma cells, obtained from effusions or solid tumours, was assayed in vitro using the multicellular tumour spheroids (MTS) three-dimensional model. Great interspecimen variabilities were observed in MTS doubling time (1.0-8.5 days), as well as in the doses inducing a 50% decrease in the MTS individual volume (ID50) (0.56-9.15 Gy), or in the overall population MTS number (SCD50) (1.9-15.7 Gy) and the residual/initial MTS individual volume ratio after 2 Gy irradiation (RSV2) (10-88%). The doubling time, DNA-ploidy and S-phase fraction did not correlate with the ID50. Significant correlations were found between the new parameters defined (RSV2 and ID50) and the SCD50, a well-accepted local control parameter. These parameters demonstrated their usefulness for studying the radiosensitivity of MTS prepared from human ovarian tumour biopsies.

Sequence-dependent growth-inhibitory effects of the in vitro combination of fluorouracil, cisplatin, and dipyridamole.

The present study was designed to analyze the growth-inhibitory effects of the combination of fluorouracil (FUra), cisplatin (CDDP), and dipyridamole (DP). These toxic effects were assessed on the human breast-carcinoma cell line MCF-7 using the MTT (tetrazolium bromide) assay in 96-well culture dishes. Data were analyzed using the median-effect principle. The drug combinations tested included FUra concentrations ranging from 0.8 to 800 nmol/l, CDDP concentrations of 0.3-30 mumol/l, and DP concentrations of 2-200 mumol/l. A total of 189 different experimental conditions were tested, including different sequences of administration, with being DP applied before, simultaneously with, or after the two antitumor drugs. Synergistic cytotoxic interactions were found between FUra and CDDP, FUra and DP, and CDDP and DP as well as when the three drugs were combined. The sequence of exposure did not influence the growth-inhibitory activity of the combination FUra-CDDP but altered the effect of combinations of either FUra or CDDP with DP, since at lower concentrations the effect shifted from synergism to antagonism when DP was added simultaneously with CDDP and after the two antitumor drugs. However, the interaction was shown to be truly synergistic by median-effect analysis when the two antitumor drugs were simultaneously associated, with no change in the synergistic effect being observed for the three DP administration sequences.