Anti-tumour activity of a panel of taxanes toward a cellular model of human cervical cancer

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.