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  • 标题:Total Flavonoids of Litsea Coreana Enhance the Cytotoxicity of Oxaliplatin by Increasing Gap Junction Intercellular Communication
  • 本地全文:下载
  • 作者:Bin-bin Yu ; Shu-ying Dong ; Mei-ling Yu
  • 期刊名称:Biological and Pharmaceutical Bulletin
  • 印刷版ISSN:0918-6158
  • 电子版ISSN:1347-5215
  • 出版年度:2014
  • 卷号:37
  • 期号:8
  • 页码:1315-1322
  • DOI:10.1248/bpb.b14-00193
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:

    Oxaliplatin is widely used in the treatment of variety of cancers, including cancer of the testis and colorectum. Gap junctions (GJs) can amplify the cytotoxicity of antinoeoplastic drugs through the bystander effect in different cancer cells. In this study, we demonstrate that total flavonoids of litsea coreana (TFLC), one extract from the dried leaves of litsea coreana leve, increase the cytotoxicity of oxaliplatin in mouse testicular cancer I-10 cells. We found that cell survival was substantially decreased only when functional GJs formed in I-10 cells. TFLC increased oxaliplatin cytotoxity (inducing cell death and apoptosis) by enhancing gap junction intercellular communication (GJIC) through elevated Cx43 protein expression. Furthermore, apoptosis-related protein (Bax, Bcl-2, caspase-3/9) results showed that the Bax/Bcl-2 ratio and activated caspase-3/9 increased when TFLC was used compared with treatment with oxaliplatin alone, which suggests that the mechanism of increased oxaliplatin-induced apoptosis was through the mitochondrial pathway. These results demonstrate that TFLC can enhance the cytotoxicity of oxaliplatin, and that these processes may be regulated in testicular tumor cells through GJ-mediated regulation of tumor cell apoptosis.

  • 关键词:litsea coreana; gap junction; apoptosis; oxaliplatin
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