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. 1999 Oct;81(4):609–615. doi: 10.1038/sj.bjc.6690737

Docetaxel and gemcitabine activity in NSCLC cell lines and in primary cultures from human lung cancer

W Zoli 1, L Ricotti 3, M Dal Susino 3, F Barzanti 3, G L Frassineti 1, S Folli 4, A Tesei 3, F Bacci 2, D Amadori 1
PMCID: PMC2362882  PMID: 10574245

Abstract

The activity of the following drugs was investigated in two established NSCLC cell lines: docetaxel, gemcitabine, vinorelbine, paclitaxel, doxorubicin (0.01, 0.1, 1 μg ml−1), cisplatin, ifosfamide (1, 2, 3 μg ml−1) and carboplatin (2, 4, 6 μg ml−1). The cytotoxic activity was evaluated by the sulphorhodamine B assay. The two most active drugs, docetaxel and gemcitabine, used singly and in association, were investigated as a function of treatment schedule. The sequence docetaxel→gemcitabine produced only a weak synergistic interaction in RAL but a strong synergism in CAEP cells. The synergistic interaction increased in both cell lines after a 48-h washout between the drug administrations. Flow cytometric analysis showed that in docetaxel→gemcitabine sequence, docetaxel produced a block in G2/M phase and, after 48 h, provided gemcitabine with a large fraction of recovered synchronized cells in the G1/S boundary, which is the specific target phase for gemcitabine. Conversely, simultaneous treatment induced an antagonistic effect in both cell lines, and the sequential scheme gemcitabine→docetaxel produced a weak synergistic effect only in RAL cells. Moreover, the synergistic interaction disappeared when washout periods of 24 or 48 h between two drug administrations were adopted. The synergistic activity of docetaxel→ 48-h washout→gemcitabine was confirmed in 11 of 14 primary cultures, which represents an important means of validating experimental results before translating them into clinical practice. © 1999 Cancer Research Campaign

Keywords: combination regimens, docetaxel, gemcitabine, NSCLC cell lines, NSCLC primary cultures, preclinical therapy

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Selected References

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