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

查看全文 作　　者：Xi-Ming Xu,Guang-Jin Yuan,Jun-Jian Deng,Hong-Ting Guo,Miao Xiang,Fang Yang,Wei Ge and Shi-You Chen Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, China ;Cancer Center, the 82nd Hospital of the Chinese PLA, Huai’an 223001, China ;Department of Physiology, Medical College of Wuhan University, Wuhan 430071, China ;Department of Physiology & Pharmacology, University of Georgia, Athens, GA 30602, USA

出　　处：《Hepatobiliary & Pancreatic Diseases International》索引2012年第11卷第2期,共10页

基　　金：supported by grants from the National Natural Science Foundation of China(81000998);the Natural Science Foundation of Hubei Province,China(2007ABA248);the Foundation of the Ministry of Education of China for New Teachers(20090141120003) 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 diethylnitrosamine-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. 关键词：HEPATOCELLULAR carcinoma 12-lipoxygenase PROLIFERATION APOPTOSIS

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

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