Document Detail

ABT-263, a Bcl-2 inhibitor, enhances the susceptibility of lung adenocarcinoma cells treated with Src inhibitors to anoikis.
MedLine Citation:
PMID:  21206976     Owner:  NLM     Status:  MEDLINE    
The tyrosine kinase Src plays an important role in the development of anoikis resistance in lung adenocarcinomas. Several suspension lung adenocarcinoma cell lines, which express phosphorylated Src, undergo apoptosis, or anoikis, in the presence of Src kinase inhibitors. However, lung adenocarcinoma cell lines vary in their sensitivity to Src inhibitors. We hypothesized that the addition of ABT-263, a potent Bcl-2 inhibitor, should significantly enhance the degree of anoikis in lung adenocarcinoma cells treated with Src inhibitors. In this study, we treated four suspension lung adenocarcinoma cell lines with ABT-263, an Src inhibitor (bosutinib or PP1), or a combination of both. In LC-KJ and HCC827 cells, combined treatment with ABT-263 and an Src inhibitor effectively induced anoikis, and the extent of anoikis was significantly greater than that induced by each agent alone; the synergy between the two drugs was apparent. Although we did not observe a marked increase in anoikis in LC-KJ and HCC827 cells treated with ABT-263 alone, H1650 and H1975 cells treated with ABT-263 (1 μM) upon detachment significantly underwent apoptosis, the levels of which were much greater than those observed upon attachment. However, the levels of anoikis induced by combination treatment were still greater than those by the individual agents in H1650 and H1975 cells. These findings provide a biological rationale to test combination therapy with ABT-263 and Src inhibitors in patients with lung adenocarcinoma.
Yuji Sakuma; Jun Tsunezumi; Yoshiyasu Nakamura; Mitsuyo Yoshihara; Shoichi Matsukuma; Shiro Koizume; Yohei Miyagi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-12-27
Journal Detail:
Title:  Oncology reports     Volume:  25     ISSN:  1791-2431     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-01-24     Completed Date:  2011-05-09     Revised Date:  2013-05-24    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  661-7     Citation Subset:  IM    
Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, 1-1-2 Nakao, Asahi-ku, Yokohama 241-0815, Japan.
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MeSH Terms
Adenocarcinoma / drug therapy,  pathology
Aniline Compounds / administration & dosage,  pharmacology*
Anoikis / drug effects*
Antineoplastic Combined Chemotherapy Protocols / pharmacology,  therapeutic use
Cell Line, Tumor
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Drug Resistance, Neoplasm / drug effects*
Drug Synergism
Lung Neoplasms / drug therapy,  pathology
Protein Kinase Inhibitors / administration & dosage,  pharmacology*
Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
Proto-Oncogene Proteins pp60(c-src) / antagonists & inhibitors*
Sulfonamides / administration & dosage,  pharmacology*
Reg. No./Substance:
0/Aniline Compounds; 0/Protein Kinase Inhibitors; 0/Proto-Oncogene Proteins c-bcl-2; 0/Sulfonamides; EC Proteins pp60(c-src); XKJ5VVK2WD/navitoclax

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