Sensitivity of non-small-cell lung cancer cell lines established from patients treated with prolonged infusions of Paclitaxel.
OBJECTIVE
Regimens with prolonged infusions of taxanes have been developed for patients with cancer to overcome drug resistance. Our objective of the present study was to examine the impact of prolonged exposure on the cytotoxicity of taxanes against non-small-cell lung carcinoma (NSCLC) cell lines and the clinical response and outcome of the patients.


METHODS
Five cell lines (NCI-H2882, -H2887, -H2973, -H3122, -H3255) were derived from previously untreated patients with NSCLC who participated in clinical trials of continuous 96-hour infusions of paclitaxel followed by bolus cisplatin. Two additional cell lines (NCI-H838, -H1299) with previously published data were used as controls. Drug sensitivities were assessed by the MTS (Promega) assay. Multidrug resistance (MDR) phenotypes were assessed by quantitative real-time PCR and HER-2/NEU by both immunohistochemistry and ELISA.


RESULTS
The median of mean IC(50) values of docetaxel at the exposure durations of 3, 24, 72 and 120 h were 0.52, 0.06, 0.03 and 0.06 microM, respectively. The median of mean IC(50) values of paclitaxel at the exposure duration of 3, 24, 72 and 120 h were 0.48, 0.13, 0.03 and 0.02 microM, respectively. In all cell lines studied, there was a less than 4-fold difference in the IC(50) values between docetaxel and paclitaxel at 3-, 72-, and 120-hour exposure times. The single cell line with moderate MDR1 expression (NCI-H2887) was the only cell line established from a patient with progressive disease when treated with paclitaxel.


CONCLUSIONS
This study demonstrates prolonged exposure to both docetaxel and paclitaxel inhibits the growth of NSCLC cell lines in similar fashion.
Fujishita
Takashi
T
Lowe Center for Thoracic Oncology, Department of Adult Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA.
Loda
Massimo
M
Turner
Ross E
RE
Gentler
Marinshine
M
Kashii
Tatsuhiko
T
Breathnach
Oscar S
OS
Johnson
Bruce E
BE
D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000188:drug therapy*; D000077143:Docetaxel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019450:Genes, MDR; D006801:Humans; D007150:Immunohistochemistry; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D043823:Taxoids; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D000077143:Docetaxel; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; C114462:multidrug resistance-associated protein 3; C421109:multidrug resistance-associated protein 1