A Study on The Mechanism of The Inhibition of Bel-7404 Hepatocarcinoma Cell Growth by MG132
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This work was supported by grants from The National Natural Science Foundation of China(30800093) and The Zhejiang Open Foundation of The Most Important Subjects(SWYX0809)

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    Abstract:

    MG132(Z-Leu-leu-leu-CHO) is an inhibitor of proteasome, and it can reversibly inhibit the activation of proteasome, thereby inhibiting the degradation of protein which involved in ubiquitin-proteasome pathway(UPP), and inducing apoptosis at last. Study demonstrated that MG132 was capable of inhibition the proliferation of Bel-7404 hepatocarcinoma cell. After treated with different-concentration of MG132 at different-time, the change of morphological change and endoplasmic reticulum stress, formation of autophagic vacuoles and apoptotic bodies, cells viability, cell apoptosis, the protein expression of both apoptosis and autophagy signaling pathway related genes formation of in Bel-7404 cells were assessed by fluorescence microscope, Hoechst33342 staining, MTT assay, AnnexinⅤ/PI flow cytometry, Western blotting and transmission electron microscopy analysis. The results suggested that MG132 can inhibit Bel-7404 cells growth remarkably . It was able to activate Caspase-12 through endoplasmic reticulum stress pathway, can also influence the level of Bcl-2/Bax, and consequently induced releasing of cytochrome c through mitochondrial pathway. Both of the two different signaling pathways can activate Caspase-3 and PARP. Furthermore, MG132 increased the expression of Beclin1 and LC3B. Autophagic vacuoles were also detected by transmission electron microscopy analysis. It was confirmed that MG132 inhibited the growth of Bel-7404 cells not only via apoptosis pathway, but also related with autophagy pathway.

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ZHANG Jing, LI Wei, ZHANG Kang-Jian, LIU Xi-Jun, KONG Yan-Ping, NIU Na, JIANG Hai, ZHOU Xiu-Mei. A Study on The Mechanism of The Inhibition of Bel-7404 Hepatocarcinoma Cell Growth by MG132[J]. Progress in Biochemistry and Biophysics,2010,37(6):627-634

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History
  • Received:September 28,2009
  • Revised:March 23,2010
  • Accepted:
  • Online: March 24,2010
  • Published: June 20,2010