Pravastatin reduces lung metastasis of rat hepatocellular carcinoma via a coordinated decrease of MMP expression and activity

Taras, Danièle; Blanc, Jean‐Frédéric; Rullier, Anne; Dugot‐Senant, Nathalie; Laurendeau, Ingrid; Vidaud, Michel; Rosenbaum, Jean

doi:10.1016/j.jhep.2006.06.015

Cited by 64 publications

(47 citation statements)

References 35 publications

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“…The hepatocarcinogenic rats were infiltrated with a large number of nodules, resulted in making the precise assessment of tumor mass impossible. The literature showed that nodules larger than 6 mm in diameter at week 24 were always hepatocarcinoma (Taras et al, 2007), so we quantified these nodules according to this standard when detectable at the surface of the liver. No hepatic nodule was observed in control non-treated, control CUR-treated or control HZC-treated group.…”

Section: Resultsmentioning

confidence: 99%

Preventive Effect of Hydrazinocurcumin on Carcinogenesis of Diethylnitrosamine-induced Hepatocarcinoma in Male SD Rats

Zhao¹,

Peng²,

Chen³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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The purpose of the present study was to evaluate the preventive effects of hydrazinocurcumin (HZC) on diethylnitrosamine (DEN)-induced hepatocarcinogenesis in a male Sprague Dawley (SD) rat model. One hundred and twenty male SD rats used in this study were divided into six groups. Those receiving DEN with curcumin (CUR) or HZC were studied compared with the DEN-alone group. The study demonstrated that DEN induced severe histological and immunohistochemical changes in liver tissues, significantly increasing the levels of liver marker enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyltransferase (GGT) and total bilirubin level (TBL)). The hepatocarcinoma incidences were 100.0%, 36.7% and 20.0% in the DEN-alone, DEN-CUR and DEN-HZC groups, respectively. Although macroscopic and microscopic features suggested that both CUR and HZC were effective in inhibiting DENinduced hepatocarcinogenesis, HZC was exerted a stronger influence. Immunohistochemical analysis with PCNA demonstrated significantly differences among the groups (all P < 0.05). Taken together, the results suggested application of CUR and HZC could prevent the occurrence of carcinogenesis and HZC may be a more potent compound for prevention of DEN-induced hepatocarcinogenesis in rats than CUR.

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Section: Resultsmentioning

confidence: 99%

Preventive Effect of Hydrazinocurcumin on Carcinogenesis of Diethylnitrosamine-induced Hepatocarcinoma in Male SD Rats

Zhao¹,

Peng²,

Chen³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…MMPs can degrade the stroma collage, which favors the action of tumor cells, leading them to shake off the yoke of ecM and migrate (24,25). it is known that MMP-2 and/or -9 levels are associated with the invasive phenotype of tumor cells (26). To further explore the possible mechanisms involved in the TGF-β1-Smad4-induced invasion and metastasis of Hcc, we examined the effects of Smad4 on the expression and activity of MMP-2 and -9 in SMMC-7721 cells.…”

Section: Discussionmentioning

confidence: 99%

Lentiviral-mediated Smad4 RNAi promotes SMMC-7721 cell migration by regulation of MMP-2, VEGF and MAPK signaling

Ji¹

2010

Mol Med Rep

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Abstract. Hepatocellular carcinoma (Hcc) is a highly malignant cancer characterized by rapid progression, easy metastasis and frequent recurrence. Previous studies have shown that the Smad4 signaling pathway plays an important role in the cell growth and apoptosis of Hcc. However, the effect of Smad4 signaling on the invasion and migration of Hcc cells remains unclear. The present study aimed to examine the effects of the transforming growth factor (TGF)-β1-Smad4 signaling pathway on the migration of Hcc cells. lentiviral vectors expressing mirna against Smad4 were constructed to block the expression of Smad4 in Hcc cells, and transwell units were used to investigate the invasive potential of SMMc-7721 cells before and after TGF-β1 treatment. mrna levels of matrix metalloproteinase (MMP)-2 and -9 were analyzed by reverse-transcription Pcr, and concentrations of vascular endothelial growth factor (VeGF), p-JnK, p-p38 and p-erk1/2 proteins were analyzed by Western blotting. The results indicate that TGF-β1 induced cellular invasion in the SMMc-7721 cells. These effects were almost completely blocked by the knockdown of Smad4. reverse-transcription Pcr and Western blot analysis revealed that MMP-2, VeGF, p-JnK and p-p38 were up-regulated by the silencing of Smad4, while the expression of MMP-9 and p-erk1/2 was not affected by Smad4 silencing with or without TGF-β1 stimulation. These findings suggest that TGF-β1-induced SMMc-7721 cell invasion by the up-regulation of MMP-2 and VeGF is Smad4-dependent. The activation of MMP-2 and VeGF may be an important mechanism by which Smad4 is involved in metastasis. TGF-β1-Smad4 signaling may regulate SMMc-7721 cell migration through the activation of the MaPK pathway.

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“…The hepatocarcinogenic rats were infiltrated with a large number of nodules, thus making the precise assessment of tumor mass impossible. The literature reports that, in previous studies, nodules measuring >6 mm in diameter at week 24 were always hepatocarcinoma (26); thus, in the present study, those nodules were quantified according to this standard when detected at the surface of the liver. As indicated in Table I, no tumors were observed in the untreated control group (group 1) or in the GL63 or CUR control groups (groups 2 and 3).…”

Section: Gl63 Potently Suppresses the Jak2/stat3 Signaling Pathway Anmentioning

confidence: 95%

A novel curcumin analogue is a potent chemotherapy candidate for human hepatocellular carcinoma

et al. 2016

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Abstract. Curcumin (CUR) has been demonstrated to protect against carcinogenesis and to prevent tumor development in cancer; however, the clinical application of CUR is limited by its instability and poor metabolic properties. The present study offers an strategy for a novel CUR analogue, (1E,4E)-1,5-bis(2-bromophenyl)penta-1,4-dien-3-one (GL63), to be used as a potential therapeutic agent for hepatocellular carcinoma (HCC) in vitro and in vivo. The current study demonstrated that GL63 exhibited more potent inhibition of proliferation of HCC cells than CUR. GL63 induced G0/G1 phase cell cycle arrest and apoptosis in SK-HEP-1 cells in a dose-dependent manner, and was more potent than CUR, according to the flow cytometry data. The present study demonstrated for the first time that the inhibition of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway by GL63 resulted in a protective effect against HCC cell growth. GL63 was more effective than CUR in regulating STAT3 downstream targets, which contributed to the suppression of cell proliferation and the induction of cell apoptosis. In addition, the effects of GL63 were tested in a model of N-nitrosodiethylamine (DEN)-induced HCC in Wistar rats. Although macroscopic and microscopic features suggested that both GL63 and CUR were effective in inhibiting DEN-induced hepatocarcinogenesis, GL63 exerted a stronger effect than CUR. Immunohistochemical analysis for proliferating cell nuclear antigen demonstrated significant differences among the DEN-bearing non-treated, DEN-bearing GL63-treated and DEN-bearing, CUR-treated groups (P=0.039). It was concluded that GL63 was a potent agent able to suppress the proliferation of HCC cells by inhibition of the JAK2/STAT3 signaling pathway, with more favorable pharmacological activity than CUR, and may be a more potent compound for the prevention of DEN-induced hepatocarcinogenesis in rats than CUR.

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Pravastatin reduces lung metastasis of rat hepatocellular carcinoma via a coordinated decrease of MMP expression and activity

Cited by 64 publications

References 35 publications

Preventive Effect of Hydrazinocurcumin on Carcinogenesis of Diethylnitrosamine-induced Hepatocarcinoma in Male SD Rats

Preventive Effect of Hydrazinocurcumin on Carcinogenesis of Diethylnitrosamine-induced Hepatocarcinoma in Male SD Rats

Lentiviral-mediated Smad4 RNAi promotes SMMC-7721 cell migration by regulation of MMP-2, VEGF and MAPK signaling

A novel curcumin analogue is a potent chemotherapy candidate for human hepatocellular carcinoma

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