Document Detail


Enhancement effect of adenovirus-mediated antisense c-myc and caffeine on the cytotoxicity of cisplatin in osteosarcoma cell lines.
MedLine Citation:
PMID:  19996588     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: Studies on cancer biology have shown that overexpression of oncogenes (with or without functional loss of tumor suppressor genes), which is responsible for the progression of human malignancies via a multistep process, may be reduced by antisense technology. Caffeine enhances the effect of cisplatin (CDDP) chemotherapy on osteosarcoma cells. We constructed the recombinant adenovirus (Myc-AS) encoding the antisense c-myc fragment and investigated the synergic effect of caffeine and Myc-AS on the in vitro sensitivity of osteosarcoma MG-63 cells to cisplatin. METHODS: The recombinant adenovirus (Myc-AS) encoding the antisense c-myc fragment was constructed by cloning c-myc cDNA of about 750 bp in a reverse direction into adenovirus vector, then undergoing recombination, amplification and complementation in vivo. Myc-AS and caffeine were used either alone or in combination with CDDP to treat osteosarcoma MG-63 cells in vitro. Western blot, MTT, flow cytometry (FCM) and electron microscopy were used to evaluate the expression of c-myc protein, tumor cell proliferation in vitro and apoptosis and to perform cell cycle analysis. RESULTS: Myc-AS encoding antisense c-myc fragment was obtained with a titer of 2 x 10(9) pfu/ml. Myc-AS downregulated the expression of c-myc protein after transfecting MG-63 cells for 48 h, induced tumor cell apoptosis and inhibited tumor cell proliferation in vitro. Myc-AS or caffeine can enhance the cytotoxic effects of 2.0 and 5.0 microg/ml CDDP on MG-63 cells. Moreover, the significantly enhancing effect of the Myc-AS-caffeine combination on CDDP chemotherapy of MG-63 cells was not restricted to apoptosis but also decreased tumor cell proliferation in vitro. Expression of the apoptosis-associated bcl-2 gene was downregulated and bax was upregulated, with no changes in E2F-1 expression. FCM analysis showed that CDDP treatment induced a block in S phase, and caffeine reversed this block and accelerated cell progression through the S phase. CONCLUSIONS: Myc-AS can induce obvious G2/M phase arrest in transfected cells. Myc-AS combined with caffeine can enhance apoptosis induction and chemotherapeutic effects of CDDP on osteosarcoma MG-63 cells.
Authors:
Xian-kuan Xie; Di-sheng Yang; Zhao-ming Ye; Hui-min Tao
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-09
Journal Detail:
Title:  Chemotherapy     Volume:  55     ISSN:  1421-9794     ISO Abbreviation:  Chemotherapy     Publication Date:  2009  
Date Detail:
Created Date:  2010-01-06     Completed Date:  2010-03-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0144731     Medline TA:  Chemotherapy     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  433-40     Citation Subset:  IM    
Copyright Information:
Copyright 2009 S. Karger AG, Basel.
Affiliation:
Department of Orthopedics, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hang Zhou, People's Republic of China. xiexkhz @ 163.com
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Caffeine / pharmacology*
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Cisplatin / pharmacology*
DNA, Antisense / administration & dosage
Drug Synergism
Flow Cytometry
Gene Expression Regulation, Neoplastic / drug effects
Genetic Vectors
Humans
Microscopy, Electron
Osteosarcoma / drug therapy,  metabolism
Proto-Oncogene Proteins c-myc / administration & dosage*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/DNA, Antisense; 0/Proto-Oncogene Proteins c-myc; 15663-27-1/Cisplatin; 58-08-2/Caffeine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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