Document Detail


Overexpression of IL-7 enhances cisplatin resistance in glioma.
MedLine Citation:
PMID:  22415136     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cisplatin is one of the most commonly used chemotherapeutic agents for glioma patients. In this study, array comparative genomic hybridization (aCGH) was used to identify genes associated with cisplatin resistance in a human glioma cell line. The cisplatin-resistant U251/CP2 cell line was derived by stepwise selection using cisplatin. The genetic aberrations of the U251 parental cell line and the U251/CP2 cells were analyzed using aCGH. RT-PCR was used to detect the expression of the altered genes revealed by aCGH. The sensitivity of glioma cells to cisplatin was determined by using the MTT assay. Apoptosis was detected using flow cytometry and western blot analysis. The IC 50 value of cisplatin in U251/CP2 cells was five times higher than its IC 50 in U251 cells. The U251 cells lost at least one copy each of the CFHR1 and CFHR3 genes, and both CFHR1 and CFHR3 were homozygously deleted in U251/CP2 cells. The U251/CP2 cells gained two to three copies of C8orf70 and IL-7 genes. IL-7 mRNA expression was studied in 12 glioma cell lines, and expression was positively correlated with the IC 50 of cisplatin. Furthermore, IL-7 mRNA expression was also positively correlated with the IC 50 of cisplatin in 91 clinical glioma specimens. Additionally, treatment with recombinant human IL-7 (rhIL-7) enhanced cisplatin resistance and increased the relative growth rate of the glioma cells. Moreover, the apoptosis induced by cisplatin could be inhibited by IL-7. In conclusion, our results suggest that IL-7 may play an important role in cisplatin resistance in glioma.
Authors:
Lei Cui; Jun Fu; Jesse Chung-Sean Pang; Zhi-Kun Qiu; Xiao-Mei Liu; Fu-Rong Chen; Hong-Liu Shi; Ho-Keung Ng; Zhong-Ping Chen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-05-01
Journal Detail:
Title:  Cancer biology & therapy     Volume:  13     ISSN:  1555-8576     ISO Abbreviation:  Cancer Biol. Ther.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-07-19     Completed Date:  2012-12-14     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  101137842     Medline TA:  Cancer Biol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  496-503     Citation Subset:  IM    
Affiliation:
State Key Laboratory of Oncology in South China and Department of Neurosurgery/Neuro-oncology, Cancer Center Sun Yat-sen University, Guangzhou, China.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects,  genetics
Cell Line, Tumor
Cell Proliferation / drug effects
Cisplatin / pharmacology*
Comparative Genomic Hybridization
Drug Resistance, Neoplasm / genetics*
Gene Expression*
Gene Expression Regulation, Neoplastic / drug effects
Glioma / drug therapy,  genetics*
Humans
Inhibitory Concentration 50
Interleukin-7 / genetics*
Transcription, Genetic
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Interleukin-7; 15663-27-1/Cisplatin
Comments/Corrections

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