| Enhancement effect of adenovirus-mediated antisense c-myc and caffeine on the cytotoxicity of cisplatin in osteosarcoma cell lines. | |
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MedLine Citation:
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PMID: 19996588 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Xian-kuan Xie; Di-sheng Yang; Zhao-ming Ye; Hui-min Tao |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-09 |
Journal Detail:
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Title: Chemotherapy Volume: 55 ISSN: 1421-9794 ISO Abbreviation: Chemotherapy Publication Date: 2009 |
Date Detail:
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Created Date: 2010-01-06 Completed Date: 2010-03-18 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0144731 Medline TA: Chemotherapy Country: Switzerland |
Other Details:
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Languages: eng Pagination: 433-40 Citation Subset: IM |
Copyright Information:
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Copyright 2009 S. Karger AG, Basel. |
Affiliation:
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Department of Orthopedics, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hang Zhou, People's Republic of China. xiexkhz @ 163.com |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae
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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:
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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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