Document Detail

Schedule-dependent antitumor activity of the combination with erlotinib and docetaxel in human non-small cell lung cancer cells with EGFR mutation, KRAS mutation or both wild-type EGFR and KRAS.
MedLine Citation:
PMID:  20878103     Owner:  NLM     Status:  MEDLINE    
Erlotinib is used as a standard treatment for recurrent advanced non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutations in NSCLC have been shown to be a predictive factor of erlotinib, although the relationship between K-ras oncogene (KRAS) mutations and erlotinib resistance is controversial. Recently, in vitro sequence-dependent interactions of erlotinib and docetaxel have been studied on as a novel therapeutic approach against NSCLC. The purpose of the present study was to determine the optimum novel regimen of erlotinib and docetaxel against NSCLC cells which have EGFR mutation (HCC827 cells), KRAS mutation (A549 cells) or both wild-type (NCI-H292 cells). First, we analyzed the effects of in vitro combination for cell proliferation-inhibition using a combination index. In all cell lines, docetaxel followed by erlotinib treatment showed nearly additive effects. On the other hand, erlotinib followed by docetaxel treatment showed remarkable antagonistic interactions. Second, we examined the effect of combinations on the in vitro apoptosis induction. Erlotinib followed by docetaxel treatment reduced apoptosis induction compared with docetaxel alone; in contrast, docetaxel followed by erlotinib treatment had no inhibitory effects on docetaxel-induced apoptosis in any of the cell lines. Finally, an in vivo tumor growth inhibition test was performed using xenograft models. Docetaxel followed by erlotinib administration resulted in significant tumor growth inhibition compared with erlotinib or docetaxel monotherapy in all models. In conclusion, we demonstrated that docetaxel followed by erlotinib therapy was a potentially optimum regimen against NSCLC regardless of the mutation status of EGFR and KRAS.
Koh Furugaki; Toshiki Iwai; Masatoshi Shirane; Kumiko Kondoh; Yoichiro Moriya; Kazushige Mori
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Oncology reports     Volume:  24     ISSN:  1791-2431     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-09-29     Completed Date:  2011-02-18     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1141-6     Citation Subset:  IM    
Product Research Department, Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd., Kamakura, Kanagawa 247-8530, Japan.
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MeSH Terms
Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
Carcinoma, Non-Small-Cell Lung / drug therapy*,  enzymology,  genetics,  pathology
Cell Growth Processes / drug effects
Cell Line, Tumor
Drug Administration Schedule
Genes, ras*
Lung Neoplasms / drug therapy*,  enzymology,  genetics,  pathology
Mice, Inbred BALB C
Quinazolines / administration & dosage
Receptor, Epidermal Growth Factor / antagonists & inhibitors,  genetics*
Taxoids / administration & dosage
Xenograft Model Antitumor Assays
Reg. No./Substance:
0/Quinazolines; 0/Taxoids; 15H5577CQD/docetaxel; EC, Epidermal Growth Factor; J4T82NDH7E/erlotinib

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