| Mey V, Giovannetti E, De Braud F, Nannizzi
S, Curigliano G, Verweij F, De Cobelli O, Pece S, Del Tacca M, Danesi
R. Division of Pharmacology and Chemotherapy, Department
of Internal Medicine, University of Pisa, 55, Via Roma, I-56100,
56126, Pisa, Italy.
The present study was performed to investigate the capability
of gemcitabine and pemetrexed to synergistically interact with
respect to cytotoxicity and apoptosis in T24 and J82 bladder cancer
cells, and to establish a correlation between drug activity and
gene expression of selected genes in tumour samples. The interaction
between gemcitabine and pemetrexed was synergistic; indeed, pemetrexed
favoured gemcitabine cytotoxicity by increasing cellular population
in S-phase, reducing Akt phosphorylation as well as by inducing
the expression of a major gemcitabine uptake system, the human
equilibrative nucleoside transporter-1 (hENT1), and the key activating
enzyme deoxycytidine kinase (dCK) in both cell lines.
Bladder tumour specimens showed an heterogeneous gene expression
pattern and patients with higher levels of dCK and hENT1 had better
response. Moreover, human nucleoside concentrative transporter-1
was detectable only in 3/12 patients, two of whom presented a
complete response to gemcitabine. These data provide evidence
that the chemotherapeutic activity of the combination of gemcitabine
and pemetrexed is synergistic against bladder cancer cells in
vitro and that the assessment of the expression of genes involved
in gemcitabine uptake and activation might be a possible determinant
of bladder cancer response and may represent a new tool for treatment
optimization.
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Pemetexed
What Is Pemetrexed?