Document Detail

Sequence-dependent synergistic inhibition of human glioma cell lines by combined Temozolomide and miR-21 inhibitor gene therapy.
MedLine Citation:
PMID:  22853427     Owner:  NLM     Status:  Publisher    
Down-regulation of microRNA-21 (miR-21) can induce cell apoptosis and reverse drug resistance in cancer treatments. In this study, we explored the most effective schedule of the miR-21 inhibitor (miR-21i) and temozolomide (TMZ) combined treatment in human glioma cells. Three tumor cell lines, U251 phosphatase and tensin homolog (PTEN) mutant, LN229 (PTEN wild-type) and U87 (PTEN loss of function) were subjected to evaluate the anti-tumor effects of deigned treatments (a predose of miR-21i for 4 h/8 h then a subsequent TMZ treatment; a predose of TMZ for 4 h/8 h then a subsequent miR-21i treatment; or a concomitant treatment) in vitro. A synergistic anti-proliferative and proapoptotic activity was only obtained in U251 and U87 cells when a predose was administered for 4 h before the treatment of the other therapeutic agent, while the best anti-tumor effect in LN229 cells was achieved by using the concomitant treatment. Our data indicate that the effect of sequence and timing of administration is dependent on PTEN status of cell lines. The best suppression effect was achieved by a maximal inhibition of STAT3 and phosphorylated STAT3, in PTEN loss of function cells. Our results reveal that both the sequence and the timing of administration are crucial in glioma combination therapy.
Xiaomin Qian; Yu Ren; Zhendong Shi; Lixia Long; Peiyu Pu; Jing Sheng; Xu-Bo Yuan; Chunsheng Kang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-1
Journal Detail:
Title:  Molecular pharmaceutics     Volume:  -     ISSN:  1543-8392     ISO Abbreviation:  Mol. Pharm.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101197791     Medline TA:  Mol Pharm     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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