Role Of PPAR γ/PTEN/MMP-9signal Pathway On Invasion And Metastasis Of Hepatocellμlar Carcinoma

hepatocellular carcinoma (hereinafter referred to as HCC) is one of the mostcommon malignant tumor, clinical accounted for5.6%of all cancers, while China is acountry liver cancer incidence and mortality rates are the highest, the number of livercancer went accounted for55%of the world.Although liver cancer basic and clinicalresearch in recent years has made a lot of progress, but it is still lack of effective earlyprevention of liver cancer and screening.Liver cancer treatment is given priority towith early surgical resection, and at the same time complementary with interventionaltherapy, ablation therapy and drug treatment, etc., but has the effect of uncertain,shortcomings and so on easy to relapse after treatment, the development of molecularbiology and liver cancer is related to the unknown.Recurrence of liver cancermortality is high, the invasion and metastasis are the most important factors affectingthe prognosis, so the mechanism of invasion and metastasis of liver cancer hasextremely important meaning to the treatment of liver cancer, is also a researchhotspot recently.In the process of invasion and metastasis of liver cancer must destroy theextracellular matrix and basement membrane, the process relies on proteindegradation enzymes, one of the main have matrix metalloproteinases (MMPs) andurokinase fibrinolytic enzyme activation system (PA).MMPs is a kind ofendopeptidase with Zn2+, almost all can degrade extracellular matrix.MMPs has beenfound that there are26members of the family, is the most important of MMP-2(collagenase A) and MMP-9(collagenase B), can degrade collagen type IV and V,laminin and other ingredients, destroy the integrity of the basement membrane.MMPsto secrete enzymes in the form of the original, need to activate the activity;The activeby the corresponding organization type of matrix metalloproteinases inhibitor (tissueinhibitors of metalloproteinases, TIMPs) inhibition.Now find TIMPs including TIMP1and TIMP-2and TIMP-3, TIMP-4four, can be combined by non covalent bondcorresponding activity of MMPS to inhibit its activity.Gao etc[1]. found by MMP-2and MMP-9, inhibits the invasion and metastasis of Huh7cells.Chen et al[2]. of92patients with liver cancer were retrospectively analyzed, found that MMP-9in HCCpatients after surgical removal of the tumor recurrence and survival prediction isbetter than that of MMP-2.Cao et al[3], such as in vitro experiment, the application ofWestern bloting method to detect human liver cancer Huh7cells PPAR gamma andPTEN protein expression, confirmed that PPAR gamma activation can be raised highinhibition gene PTEN expression.PPAR gamma raised PTEN expression after highactivation energy[4], thereby inhibition of PI3K/AKT pathway, and PI3K/PTEN/AKTpathway is involved in liver cancer cell invasion and metastasis process and related to the expression of matrix metalloproteinases (MMPS).Further studies have found thatspecific antagonism PPAR gamma signal the invasion and metastasis is closely relatedto the protein can inhibit the activation of MMP-9.Zhou[5]reports on propofolthrough PI3K/Akt signal to reduce liver matrix metalloproteinases levels, to suppressliver cancer cell migration and invasion.But whether the MMP-9participate in PPARgamma inhibiting liver cancer invasion and metastasis process? The existence ofPPAR gamma/PTEN/MMP-9pathway, still needs further research.Objective To investigate whether PPARγ/PTEN/MMP-9signaling pathway inhepatocellular carcinoma, and PTEN and matrix metalloproteinase-9(MMP-9)changes, to further clarify the role of this signaling pathway on invasion andmetastasis of hepatocellular carcinoma cells.Methods the cultured SMMC-7721cells, the PPARγ natural ligand of15-deoxyprostaglandin J2(15-d-PGJ2) and the inhibitor of GW9662,the viability of hepatomacells measured by MTT method, the migration ability by wound healing assay andTranswell method; detection of cells with expression PTEN and MMP-9mRNA byRT-PCR；PTEN and MMP-9protein expression were detected by Western blot.Results15-d-PGJ2can inhibit the proliferation of hepatoma cells, in adose-dependent manner, increase the expression of PTEN mRNA and protein inSMMC-7721cells, and reduce the expression of MMP-9mRNA and protein.ButGW9662had no effect.Conclusion hepatocellular carcinoma in PPARγ/PTEN/MMP-9signaling pathway,through the up regulation of PTEN and down-regulation of MMP-9expression,inhibition of invasion and metastasis of hepatoma cells.