TY - JOUR
T1 - Schedule-dependent interaction between the proteosome inhibitor bortezomib and the EGFR-TK inhibitor erlotinib in human non-small cell lung cancer cell lines
AU - Piperdi, Bilal
AU - Ling, Yi He
AU - Perez-Soler, Roman
PY - 2007/8
Y1 - 2007/8
N2 - INTRODUCTION: Both erlotinib (E) and bortezomib (B) have shown single-agent activity in patients with non-small cell lung cancer. We studied the combination of these two novel biologic agents in vitro using a panel of non-small cell lung cancer cell lines. METHODS: The growth inhibitory effect of E and B were determined by MTT assay on seven non-small cell lung cancer cell lines. The data obtained from the growth inhibition assay in response to the combination of E and B were subject to isobologram analysis. The effects of each individual drug as well as combination in different sequences on cell cycle and apoptosis were determined by flow cytometry. RESULTS: Two of seven cell lines are sensitive to E. However, B has narrower range of cytotoxicity. The combination is neither synergistic nor additive in two of four cell lines tested. In H358 bronchoalveolar cell lines, the combination is more active than either agent alone. E causes G1 cell cycle arrest and B causes G2/M cell cycle arrest. In sequential studies, 24-hour previous exposure to E causes G1 arrest and abrogates the cytotoxic effect of B. This is observed in both E-sensitive as well as E-resistant cells and is accompanied by an increase in cell survival and a decrease in apoptosis. CONCLUSIONS: The combination of E and B is neither additive nor synergistic in two of four cell lines tested. In H358 bronchoalveolar cell, the combination is more active than either agent alone. The schedule-dependent antagonistic effect of E pre-exposure was observed. E pre-exposure causes G1 cell cycle arrest and abrogates the activity of B. Further in vivo studies of this combination are warranted.
AB - INTRODUCTION: Both erlotinib (E) and bortezomib (B) have shown single-agent activity in patients with non-small cell lung cancer. We studied the combination of these two novel biologic agents in vitro using a panel of non-small cell lung cancer cell lines. METHODS: The growth inhibitory effect of E and B were determined by MTT assay on seven non-small cell lung cancer cell lines. The data obtained from the growth inhibition assay in response to the combination of E and B were subject to isobologram analysis. The effects of each individual drug as well as combination in different sequences on cell cycle and apoptosis were determined by flow cytometry. RESULTS: Two of seven cell lines are sensitive to E. However, B has narrower range of cytotoxicity. The combination is neither synergistic nor additive in two of four cell lines tested. In H358 bronchoalveolar cell lines, the combination is more active than either agent alone. E causes G1 cell cycle arrest and B causes G2/M cell cycle arrest. In sequential studies, 24-hour previous exposure to E causes G1 arrest and abrogates the cytotoxic effect of B. This is observed in both E-sensitive as well as E-resistant cells and is accompanied by an increase in cell survival and a decrease in apoptosis. CONCLUSIONS: The combination of E and B is neither additive nor synergistic in two of four cell lines tested. In H358 bronchoalveolar cell, the combination is more active than either agent alone. The schedule-dependent antagonistic effect of E pre-exposure was observed. E pre-exposure causes G1 cell cycle arrest and abrogates the activity of B. Further in vivo studies of this combination are warranted.
UR - http://www.scopus.com/inward/record.url?scp=34548402083&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548402083&partnerID=8YFLogxK
U2 - 10.1097/JTO.0b013e3180f60bb3
DO - 10.1097/JTO.0b013e3180f60bb3
M3 - Article
C2 - 17762337
AN - SCOPUS:34548402083
SN - 1556-0864
VL - 2
SP - 715
EP - 721
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 8
ER -