首页> 中文期刊> 《国际肝胆胰疾病杂志(英文版)》 >Inhibition of 12-lipoxygenase reduces proliferation and induces apoptosis of hepatocellular carcinoma cells in vitro and in vivo

Inhibition of 12-lipoxygenase reduces proliferation and induces apoptosis of hepatocellular carcinoma cells in vitro and in vivo

         

摘要

BACKGROUND: 12-lipoxygenase (12-LOX) has been reported to be an important gene in cancer cell proliferation and survival, and  tumor  metastasis.  However,  its  role  in  hepatocellular carcinoma (HCC) cells remains unknown. METHODS: Expression  of  12-LOX  was  assessed  in a diethyl-nitrosamine-induced  rat  HCC  model,  and  in  SMMC-7721, HepG2  and  L-02  cells  using  immunohistochemical  staining and  reverse  transcriptase-polymerase  chain  reaction (RT-PCR).  GST-π  and  Ki-67  were  determined  in vivo  by immunohistochemical  staining.  Apoptosis  was  evaluated  by TUNEL assay. Cell viability and apoptosis were determined by MTT assay and flow cytometry, respectively. Apoptosis-related proteins  in  SMMC-7721  and  HepG2  cells  were  detected  by Western blotting. RESULTS: Immunohistochemical staining and RT-PCR showed that 12-LOX was over-expressed in rat HCC and two HCC cell lines, while the expression was inhibited by baicalein, a specific inhibitor of 12-LOX. Baicalein inhibited cell proliferation and induced apoptosis in rat HCC and both cell lines in a dose- and time-dependent manner. Our in vivo study demonstrated that baicalein  also  reduced  neoplastic  nodules.  Mechanistically, baicalein reduced Bcl-2 protein expression coupled with a slight increase  of  the  expression  of  Bax  and  activation  of  caspase-3. Furthermore,  baicalein  inhibited  the  activation  of  ERK-1/2 (phosphorylated).  Interestingly,  the  effects  of  baicalein  were reversed by 12(S)-HETE, a metabolite of 12-LOX. CONCLUSIONS: Inhibition  of  12-LOX  leads  to  reduced numbers of HCC cells, partially caused by increased apoptosis. 12-LOX may be a potential molecular target for HCC prevention and treatment.

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  • 来源
    《国际肝胆胰疾病杂志(英文版)》 |2012年第2期|81-90|共10页
  • 作者单位

    Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, China Xu XM, Deng JJ, Guo HT, Xiang M and Ge W;

    Cancer Center, the 82nd Hospital of the Chinese PLA, Huai'an 223001, China Yuan GJ;

    Department of Physiology, Medical College of Wuhan University, Wuhan 430071, China Yang F;

    Department of Physiology & Pharmacology, University of Georgia, Athens, GA 30602, USA Chen SY;

    Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, China Xu XM, Deng JJ, Guo HT, Xiang M and Ge W;

    Cancer Center, the 82nd Hospital of the Chinese PLA, Huai'an 223001, China Yuan GJ;

    Department of Physiology, Medical College of Wuhan University, Wuhan 430071, China Yang F;

    Department of Physiology & Pharmacology, University of Georgia, Athens, GA 30602, USA Chen SY;

    Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, China Xu XM, Deng JJ, Guo HT, Xiang M and Ge W;

    Cancer Center, the 82nd Hospital of the Chinese PLA, Huai'an 223001, China Yuan GJ;

    Department of Physiology, Medical College of Wuhan University, Wuhan 430071, China Yang F;

    Department of Physiology & Pharmacology, University of Georgia, Athens, GA 30602, USA Chen SY;

    Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, China Xu XM, Deng JJ, Guo HT, Xiang M and Ge W;

    Cancer Center, the 82nd Hospital of the Chinese PLA, Huai'an 223001, China Yuan GJ;

    Department of Physiology, Medical College of Wuhan University, Wuhan 430071, China Yang F;

    Department of Physiology & Pharmacology, University of Georgia, Athens, GA 30602, USA Chen SY;

    Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, China Xu XM, Deng JJ, Guo HT, Xiang M and Ge W;

    Cancer Center, the 82nd Hospital of the Chinese PLA, Huai'an 223001, China Yuan GJ;

    Department of Physiology, Medical College of Wuhan University, Wuhan 430071, China Yang F;

    Department of Physiology & Pharmacology, University of Georgia, Athens, GA 30602, USA Chen SY;

    Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, China Xu XM, Deng JJ, Guo HT, Xiang M and Ge W;

    Cancer Center, the 82nd Hospital of the Chinese PLA, Huai'an 223001, China Yuan GJ;

    Department of Physiology, Medical College of Wuhan University, Wuhan 430071, China Yang F;

    Department of Physiology & Pharmacology, University of Georgia, Athens, GA 30602, USA Chen SY;

    Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, China Xu XM, Deng JJ, Guo HT, Xiang M and Ge W;

    Cancer Center, the 82nd Hospital of the Chinese PLA, Huai'an 223001, China Yuan GJ;

    Department of Physiology, Medical College of Wuhan University, Wuhan 430071, China Yang F;

    Department of Physiology & Pharmacology, University of Georgia, Athens, GA 30602, USA Chen SY;

    Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, China Xu XM, Deng JJ, Guo HT, Xiang M and Ge W;

    Cancer Center, the 82nd Hospital of the Chinese PLA, Huai'an 223001, China Yuan GJ;

    Department of Physiology, Medical College of Wuhan University, Wuhan 430071, China Yang F;

    Department of Physiology & Pharmacology, University of Georgia, Athens, GA 30602, USA Chen SY;

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