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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-4-3
pubmed:abstractText
Gefitinib, a low-molecular-weight epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is effective in a wide variety of tumor types. Preclinical studies have shown potentiated antitumor efficacies of this agent in combination with chemotherapy or radiotherapy. The antitumor antibiotic lidamycin (LDM) showed extremely potent cytotoxicity in vitro and marked therapeutic effect in vivo. In this report, the cytotoxic and biochemical activity of LDM and gefitinib on human epidermoid carcinoma A431 cells and human large cell lung cancer H460 cells as a single agent or in combination has been evaluated. In the MTT assay, LDM showed much more potent cytotoxicity than gefitinib to both cell lines. A431 cells with a highly EGFR-expressing level were more sensitive to gefitinib than H460 cells, which expressed EGFR at an intermediate level. LDM plus gefitinib showed potentiation of antiproliferative activity and apoptosis induction, which were associated with downregulation of EGFR signaling pathway and nuclear factor-kappa B expression, and the increase of cleaved poly (adenosine diphosphate-ribose) polymerase in the two cell lines, although to a lesser degree in H460 cells. Combined treatment induced G1 phase arrest similar to that of gefitinib alone in A431 cells and intensified G2/M phase accumulation in H460 cells. The above results indicate that LDM potentiates the effects of gefitinib in both gefitinib sensitive and less sensitive cells in association with enhanced inhibition of EGFR-dependent signaling.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1473-5741
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
41-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:19342999-Aminoglycosides, pubmed-meshheading:19342999-Antibiotics, Antineoplastic, pubmed-meshheading:19342999-Antineoplastic Agents, pubmed-meshheading:19342999-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:19342999-Apoptosis, pubmed-meshheading:19342999-Carcinoma, pubmed-meshheading:19342999-Carcinoma, Squamous Cell, pubmed-meshheading:19342999-Cell Cycle, pubmed-meshheading:19342999-Cell Line, Tumor, pubmed-meshheading:19342999-Cell Proliferation, pubmed-meshheading:19342999-Cell Survival, pubmed-meshheading:19342999-Dose-Response Relationship, Drug, pubmed-meshheading:19342999-Drug Synergism, pubmed-meshheading:19342999-Enediynes, pubmed-meshheading:19342999-Humans, pubmed-meshheading:19342999-Lung Neoplasms, pubmed-meshheading:19342999-Phosphorylation, pubmed-meshheading:19342999-Protein Kinase Inhibitors, pubmed-meshheading:19342999-Quinazolines, pubmed-meshheading:19342999-Receptor, Epidermal Growth Factor, pubmed-meshheading:19342999-Signal Transduction
pubmed:year
2009
pubmed:articleTitle
Enediyne lidamycin enhances the effect of epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib, in epidermoid carcinoma A431 cells and lung carcinoma H460 cells.
pubmed:affiliation
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't