Epithelial-mesenchymal transition （EMT） is initially considered as a physiological phenomenon during the embryogenesis of mammals, as well as a basic biological event maintaining the stability of the vital body. Recent researches indicated that EMT plays a critical role in various tumors progression, through which epithelial cancers invade and metastasize. The cell characteristics are changed during EMT, in which the cells lose cell-cell and cell-matrix interactions and apical polarity, reorganize their cytoskeleton, and become isolated, motile, as well as resistant to anoikis, then become spindle-shaped mesenchymal cells. This review lays emphasis on studying the cell morphogenesis, makers and molecular mechanism regulation about EMT, discussing the relationship between the EMT and the cancer development and metastasis.
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.
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
