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

W. Zoli, L. Ricotti, M. Dal Susino, F. Barzanti, G. L. Frassineti, S. Folli, A. Tesei, F. Bacci, D. Amadori

Research output: Contribution to journalArticle

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 G2M 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.

Original languageEnglish
Pages (from-to)609-615
Number of pages7
JournalBritish Journal of Cancer
Volume81
Issue number4
DOIs
Publication statusPublished - 1999

Fingerprint

docetaxel
gemcitabine
Lung Neoplasms
Cell Line
lissamine rhodamine B
Pharmaceutical Preparations
Ifosfamide
Carboplatin
Paclitaxel
Doxorubicin
Cisplatin
Appointments and Schedules

Keywords

  • Combination regimens
  • Docetaxel
  • Gemcitabine
  • NSCLC cell lines
  • NSCLC primary cultures
  • Preclinical therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Docetaxel and gemcitabine activity in NSCLC cell lines and in primary cultures from human lung cancer. / Zoli, W.; Ricotti, L.; Dal Susino, M.; Barzanti, F.; Frassineti, G. L.; Folli, S.; Tesei, A.; Bacci, F.; Amadori, D.

In: British Journal of Cancer, Vol. 81, No. 4, 1999, p. 609-615.

Research output: Contribution to journalArticle

Zoli, W. ; Ricotti, L. ; Dal Susino, M. ; Barzanti, F. ; Frassineti, G. L. ; Folli, S. ; Tesei, A. ; Bacci, F. ; Amadori, D. / Docetaxel and gemcitabine activity in NSCLC cell lines and in primary cultures from human lung cancer. In: British Journal of Cancer. 1999 ; Vol. 81, No. 4. pp. 609-615.
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