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Dysfunction of volume-sensitive chloride channels contributes to cisplatin resistance in human lung adenocarcinoma cells.
MedLine Citation:
PMID:  21454376     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cisplatin-based chemotherapy is the standard therapy used to treat non-small-cell lung cancer. However, its efficacy is largely limited due to the development of drug resistance. The exact mechanism in which cancer cells develop resistance to the drug is not yet fully understood. The purpose of the present study is to test the role of volume-sensitive Cl(-) channels in cisplatin resistance in human lung adenocarcinoma cells (A549 cells) using patch-clamp recording, cell volume measurement and apoptosis assay. The results showed that cisplatin treatment induced an apoptotic volume decrease (AVD) and activated a Cl(-) current that showed properties similar to the volume-sensitive outward rectifying (VSOR) Cl(-) current in wild-type A549 cells. Both the AVD process and VSOR Cl(-) current were blocked by the chloride channel blocker 4,4'-diisothiocyanostilbene-2,2' disulfonic acid. However, the A549/CDDP cells, a model of acquired cisplatin resistance cells, on the other hand, had almost no AVD process and VSOR Cl(-) current when treated with cisplatin. Treatment of A549/CDDP cells with trichostatin A (TSA), a drug that inhibits histone deacetylases, partially restored the VSOR Cl(-) current and increased cisplatin-induced cell apoptosis rate. These results suggest that impaired activity of VSOR Cl(-) channels contributes to the cisplatin resistance in A549/CDDP cells.
Authors:
Xian-Jun Min; Hui Li; Sheng-Cai Hou; Wei He; Jie Liu; Bin Hu; Jun Wang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-31
Journal Detail:
Title:  Experimental biology and medicine (Maywood, N.J.)     Volume:  -     ISSN:  1535-3699     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-4-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100973463     Medline TA:  Exp Biol Med (Maywood)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Capital Medical University, Beijing 100069.
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