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 language | English |
|---|---|
| Pages (from-to) | 609-615 |
| Number of pages | 7 |
| Journal | British Journal of Cancer |
| Volume | 81 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 1999 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Docetaxel and gemcitabine activity in NSCLC cell lines and in primary cultures from human lung cancer
AU - Zoli, W.
AU - Ricotti, L.
AU - Dal Susino, M.
AU - Barzanti, F.
AU - Frassineti, G. L.
AU - Folli, S.
AU - Tesei, A.
AU - Bacci, F.
AU - Amadori, D.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
KW - Combination regimens
KW - Docetaxel
KW - Gemcitabine
KW - NSCLC cell lines
KW - NSCLC primary cultures
KW - Preclinical therapy
UR - http://www.scopus.com/inward/record.url?scp=0032885543&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032885543&partnerID=8YFLogxK
U2 - 10.1038/sj.bjc.6690737
DO - 10.1038/sj.bjc.6690737
M3 - Article
C2 - 10574245
AN - SCOPUS:0032885543
VL - 81
SP - 609
EP - 615
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 4
ER -