Document Detail

Identification of carbonic anhydrase 9 as a contributor to pingyangmycin-induced drug resistance in human tongue cancer cells.
MedLine Citation:
PMID:  21040473     Owner:  NLM     Status:  MEDLINE    
Drug resistance is the major obstacle to successful cancer treatment. To understand the mechanisms responsible for drug resistance in tongue cancer, Tca8113 cells derived from moderately differentiated human tongue squamous cell carcinoma were exposed to stepwise escalated concentrations of pingyangmycin (PYM) to develop the resistant cell line called Tca8113/PYM, which showed over 18.78-fold increased resistance to PYM as compared with Tca8113 cells, and cross-resistance to cisplatin, pirarubicin, paclitaxel, adriamycin, and mitomycin. We found that the resistance was not associated with multidrug resistance transporter 1 (p170, p-gp), multidrug resistance-associated protein 1 and breast cancer resistance protein overexpression, so we hypothesized that Tca8113/PYM cells must have some other resistance mechanism selected by PYM. To test this hypothesis, the global gene expression profiles between Tca8113 and Tca8113/PYM cells were compared by cDNA microarray. Eighty-nine genes and thirteen expressed sequence tags with differential expression levels between the two cell lines were identified. Some differential expression levels were validated with real-time PCR and western blot. Furthermore, the functional validation showed that both carbonic anhydrase (CA) inhibitor acetazolamide application and CA9 silencing with CA9 antisense oligonucleotides contribute to the medium pH increase of Tca8113/PYM cells and enhanced PYM chemosensitivity. Moreover, both acetazolamide and CA9 antisense oligonucleotides significantly increased PYM-induced caspase 3 activation in Tca8113/PYM cells. Thus, our study suggests that the resistance of Tca8113/PYM cells is probably associated with CA9 and other differential expression molecules, and that CA9 may be an important marker for prediction of PYM responsiveness in tongue cancer chemotherapy.
Guopei Zheng; Min Zhou; Xinrong Ou; Bo Peng; Yanhui Yu; Fangren Kong; Yongmei Ouyang; Zhimin He
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-04
Journal Detail:
Title:  The FEBS journal     Volume:  277     ISSN:  1742-4658     ISO Abbreviation:  FEBS J.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-02     Completed Date:  2010-12-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  England    
Other Details:
Languages:  eng     Pagination:  4506-18     Citation Subset:  IM    
Copyright Information:
© 2010 The Authors Journal compilation © 2010 FEBS.
Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
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MeSH Terms
Acetazolamide / pharmacology
Antibiotics, Antineoplastic / pharmacology
Antigens, Neoplasm / genetics,  metabolism*
Bleomycin / analogs & derivatives*,  pharmacology
Blotting, Western
Carbonic Anhydrases / genetics,  metabolism*
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Dose-Response Relationship, Drug
Drug Resistance, Multiple
Drug Resistance, Neoplasm*
Gene Expression Profiling
Gene Expression Regulation, Neoplastic / drug effects
Oligonucleotide Array Sequence Analysis
Oligonucleotides, Antisense / genetics
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Tongue Neoplasms / genetics,  metabolism,  pathology
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Antigens, Neoplasm; 0/Oligonucleotides, Antisense; 11056-06-7/Bleomycin; 11116-32-8/bleomycetin; 59-66-5/Acetazolamide; EC protein, human; EC Anhydrases

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