Using a model of human cervical cancer (ME-180 cells), the anti-tumour acti
vity of paclitaxel was compared to that of docetaxel and IDN5109, a, newly
developed taxane. The growth inhibition effect of taxanes was assessed afte
r 3 days of exposure. DNA analysis, the taxane-dependent modulation of the
expression of the alpha and beta 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 int
ravenously once daily, according to a q3/4d x 4 schedule. Docetaxel, IDN510
9 and paclitaxel obtained "in vitro" IC50 values of 0.86, 1.4 and 2.4 nM, r
espectively. DNA analysis demonstrated a transient block at the G(2)/M phas
e of the cell cycle only after 12 h of culture in the presence of taxanes a
nd an increase of nuclear fragmentation suggestive for apoptosis after addi
tional 12 and 60 h of exposure. Morphological analysis confirmed the presen
ce of apoptosis. Taxanes induced a down-modulation of the a subunit of; tub
ulin in the G(0/1) phase of the cell cycle, and an overexpression of the be
ta subunit in the G(2)/M phase. A strong anti-tumour activity was obtained
"in vive" for nude mice xenografted using ME-180 cells (T/C = 0% for all dr
ugs). These data indicate that the three taxanes are strongly active both "
in vitro" and "in vive" toward ME-180 cells. Clinical studies are now neede
d to ascertain if the higher anti-tumour activity observed "in vitro" using
docetaxel and IDN5109 yields a better clinical response in advanced cervic
al carcinoma with respect to paclitaxel.