TY - JOUR
T1 - Paclitaxel (Taxol®) inhibits motility of paclitaxel-resistant human ovarian carcinoma cells
AU - Belotti, Dorina
AU - Rieppi, Monica
AU - Nicoletti, Maria Ines
AU - Casazza, Anna Maria
AU - Fojo, Tito
AU - Taraboletti, Giulia
AU - Giavazzi, Ratfaella
PY - 1996/10
Y1 - 1996/10
N2 - The effect of paclitaxel on the adhesive and motility properties of human ovarian carcinoma cell lines was investigated. Paclitaxel significantly inhibited the motility of OVCAR 5, SK-OV-3, and HOC-1OTC ovarian carcinoma cell lines (IC50 = 2.1 x 10-8, 2 x 10-9, and 1.9 x 10-8 M, respectively) but did not affect the adhesion of these cells to the subendothelial matrix. The association between inhibition of motility and cytotoxic activity was investigated using an A2780 subclone (1A9) and three paclitaxel-resistant variants (designated 1A9/PTX22, 1A9/PTX10, and 1A9/PTX18). Although paclitaxel did not significantly affect the adhesion to subendothelial matrix of the sublines, it completely inhibited their migration. Inhibition of migration was similar in 1A9 cells and the resistant sublines. with an IC50 of 1 x 10-8 for 1A9 cells and 5.4 x 10-9, 1.1 x 10-8, and 5.2 x 10-9 M for 1A9/PTX22, 1A9/PTX10, and 1A9/PTX18, respectively. Paclitaxel inhibited motility induced by soluble attractant (chemotaxis) and immobilized attractant (haptotaxis). Inhibition of cell motility occurred in the absence of an antiproliferative effect, because higher concentrations of paclitaxel were required to inhibit tumor cell proliferation (IC50 = 1.9 x 10-7 and 4.6 x 10-6, 1 x 10-5, and 3.1 x 10-6 M for 1A9 and 1A9/PTX22, 1A9/PTX10, and 1A9/PTX18, respectively). These data show that paclitaxel is a potent inhibitor of ovarian carcinoma cell motility and that this activity is independent of its cytotoxic activity.
AB - The effect of paclitaxel on the adhesive and motility properties of human ovarian carcinoma cell lines was investigated. Paclitaxel significantly inhibited the motility of OVCAR 5, SK-OV-3, and HOC-1OTC ovarian carcinoma cell lines (IC50 = 2.1 x 10-8, 2 x 10-9, and 1.9 x 10-8 M, respectively) but did not affect the adhesion of these cells to the subendothelial matrix. The association between inhibition of motility and cytotoxic activity was investigated using an A2780 subclone (1A9) and three paclitaxel-resistant variants (designated 1A9/PTX22, 1A9/PTX10, and 1A9/PTX18). Although paclitaxel did not significantly affect the adhesion to subendothelial matrix of the sublines, it completely inhibited their migration. Inhibition of migration was similar in 1A9 cells and the resistant sublines. with an IC50 of 1 x 10-8 for 1A9 cells and 5.4 x 10-9, 1.1 x 10-8, and 5.2 x 10-9 M for 1A9/PTX22, 1A9/PTX10, and 1A9/PTX18, respectively. Paclitaxel inhibited motility induced by soluble attractant (chemotaxis) and immobilized attractant (haptotaxis). Inhibition of cell motility occurred in the absence of an antiproliferative effect, because higher concentrations of paclitaxel were required to inhibit tumor cell proliferation (IC50 = 1.9 x 10-7 and 4.6 x 10-6, 1 x 10-5, and 3.1 x 10-6 M for 1A9 and 1A9/PTX22, 1A9/PTX10, and 1A9/PTX18, respectively). These data show that paclitaxel is a potent inhibitor of ovarian carcinoma cell motility and that this activity is independent of its cytotoxic activity.
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M3 - Article
C2 - 9816123
AN - SCOPUS:0029657597
VL - 2
SP - 1725
EP - 1730
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 10
ER -