Sensitivity of Non-Small-Cell Lung Cancer Cell Lines Established from Patients Treated with Prolonged Infusions of Paclitaxel

Abstract

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 IC₅₀ values of docetaxel at the exposure durations of 3, 24, 72 and 120 h were 0.52, 0.06, 0.03 and 0.06 µM, respectively. The median of mean IC₅₀ values of paclitaxel at the exposure duration of 3, 24, 72 and 120 h were 0.48, 0.13, 0.03 and 0.02 µM, respectively. In all cell lines studied, there was a less than 4-fold difference in the IC₅₀ 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.

Gefitinib Induces Apoptosis in the EGFRL858R Non–Small-Cell Lung Cancer Cell Line H3255

“…Constitutive AKT activation has also been associated with resistance to chemotherapy and radiation in NSCLC cell lines (21). We have also demonstrated previously that the H3255 cell line is resistant to paclitaxel and docetaxel in vitro (7). It is thus possible that chemotherapy will be less effective in patients whose tumors contain EGFR L858R than in those with a wild-type EGFR.…”

“…Three BAC [NCI-H358, NCI-H1666, and NCI-H1781 (referred to henceforth as H358, H1666, and H1781, respectively)] and six adenocarcinoma cell lines [NCI-A549, NCI-H23, NCI-H441, NCI-H2347, NCI-H3122, and NCI-H3255 (referred to henceforth as A549, H23, H441, H2347, H3122, and H3255, respectively)] were used in this study and were either purchased from American Type Culture Collection or obtained from the National Cancer Institute and have been characterized previously (5,7). Cell lines were maintained as described previously (5).…”

PF00299804, an Irreversible Pan-ERBB Inhibitor, Is Effective in Lung Cancer Models withEGFRandERBB2Mutations that Are Resistant to Gefitinib

“…The EGFR mutant NSCLC cell lines H3255 (L858R), HCC827 (del E746_A750) and H1975 (L858R/T790M), HCC820 (del 747_L751, Ins S/T790M), HCC4006 (Del L747_E749), and PC-9 (Del E746_A750) were used in this study and have been extensively characterized (5,13,(26)(27)(28)(29)(30). H3255 GR were selected in vitro for their resistance to gefitinib, contain an EGFR T790M in cis with L858R in a limited number of alleles, and have been previously characterized (23).…”

Activated Epidermal Growth Factor Receptor–Stat-3 Signaling Promotes Tumor SurvivalIn vivoin Non–Small Cell Lung Cancer

“…Human NSCLC cell lines were purchased from American Type Culture Collection (ATCC; Manassas, VA). H3255 cells were provided by Dr. Pasi Janne and grown as previously described (25). All other cells were grown in RPMI 1640 supplemented with 2 mmol/L L-glutamine (Santa Cruz Biotechnology, Santa Cruz, CA) and 5% bovine calf serum (Hyclone).…”