Paclitaxel (Taxol®) inhibits motility of paclitaxel-resistant human ovarian carcinoma cells

Dorina Belotti, Monica Rieppi, Maria Ines Nicoletti, Anna Maria Casazza, Tito Fojo, Giulia Taraboletti, Ratfaella Giavazzi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1725-1730
Number of pages6
JournalClinical Cancer Research
Volume2
Issue number10
Publication statusPublished - Oct 1996

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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