Abstract
Using a model of human cervical cancer (ME-180 cells), the anti-tumour activity of paclitaxel was compared to that of docetaxel and IDN5109, a newly developed taxane. The growth inhibition effect of taxanes was assessed after 3 days of exposure. DNA analysis, the taxane-dependent modulation of the expression of the α and β subunits of tubulin and DNA fragmentation were assessed by flow cytometry. The presence of apoptosis was confirmed by morphological analysis using a laser scan cytometer. For the evaluation of “in vivo” anti-tumour activity, taxanes were administered to nude mice intravenously once daily, according to a q3/4d × 4 schedule. Docetaxel, IDN5109 and paclitaxel obtained “in vitro” IC50 values of 0.86, 1.4 and 2.4 nM, respectively. DNA analysis demonstrated a transient block at the G2/M phase of the cell cycle only after 12 h of culture in the presence of taxanes and an increase of nuclear fragmentation suggestive for apoptosis after additional 12 and 60 h of exposure. Morphological analysis confirmed the presence of apoptosis. Taxanes induced a down-modulation of the α subunit of tubulin in the G0/1 phase of the cell cycle, and an overexpression of the β subunit in the G2/M phase. A strong anti-tumour activity was obtained “in vivo” for nude mice xenografted using ME-180 cells (T/C=0% for all drugs). These data indicate that the three taxanes are strongly active both “in vitro” and “in vivo” toward ME-180 cells. Clinical studies are now needed to ascertain if the higher anti-tumour activity observed “in vitro” using docetaxel and IDN5109 yields a better clinical response in advanced cervical carcinoma with respect to paclitaxel.
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Received: 4 May 1999 / Accepted: 9 July 1999
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Gallo, D., Ferlini, C., Distefano, M. et al. Anti-tumour activity of a panel of taxanes toward a cellular model of human cervical cancer. Cancer Chemother Pharmacol 45, 127–132 (2000). https://doi.org/10.1007/s002800050020
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DOI: https://doi.org/10.1007/s002800050020