Dataset Information

Bufalin attenuates the stage and metastatic potential of hepatocellular carcinoma in nude mice.

ABSTRACT: Advanced hepatocellular carcinoma (HCC) patients undergo significant tumor growth and metastasis. Here, we investigated bufalin for treating HCC, which exhibits anti-tumor activities in many tumor cell lines.In our experiment, HCCLM3-R cells were injected into nude mice to form subcutaneous human HCC tumors that were implanted into the liver to establish orthotopic transplantation tumor models. Bufalin was injected intraperitoneally at 1 or 1.5 mg/kg. LY294002 (100 mg/kg), a potent inhibitor of Akt which reduced the levels of pAkt in HCCLM3 cell lines, was injected intraperitoneally into one group thrice weekly. The control was injected with an equal volume of saline. Morphological alterations were evaluated in the liver and lung by stereomicroscopy, the apoptotic rate was measured by TUNEL staining, and expression of AKT/GSK3?/?-catenin/E-cadherin signaling pathway-related proteins was detected by immunohistochemistry (IHC) and western blot analysis.These results suggested that the sizes and qualities of orthotopic transplanted tumors as well as pulmonary metastasis decreased markedly at the highest bufalin dose compared with that in the control. Orthotopic transplanted tumor tissues were necrotic in bufalin-treated groups and the apoptotic cell number was markedly higher at the highest bufalin dose compared with that in the control. Certain changes of expression of AKT/GSK3?/?-catenin/E-cadherin signaling pathway-related proteins were in tumor tissues, which were related to the bufalin dose. Similar results were observed in the LY294002-treated group.Based on the above, one can draw conclusions that bufalin has significant anti-tumor activities and reduces the metastatic potential in an orthotopic transplantation tumor model of human HCC. Inhibition of AKT/GSK3?/?-catenin/E-cadherin signaling pathways by bufalin may show therapeutic effects in advanced HCC patients.

SUBMITTER: Zhang ZJ

PROVIDER: S-EPMC4015709 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Bufalin attenuates the stage and metastatic potential of hepatocellular carcinoma in nude mice.

Zhang Zhou-Ji ZJ Yang Yun-Ke YK Wu Wei-Zhong WZ

Journal of translational medicine 20140228

<h4>Background</h4>Advanced hepatocellular carcinoma (HCC) patients undergo significant tumor growth and metastasis. Here, we investigated bufalin for treating HCC, which exhibits anti-tumor activities in many tumor cell lines.<h4>Method</h4>In our experiment, HCCLM3-R cells were injected into nude mice to form subcutaneous human HCC tumors that were implanted into the liver to establish orthotopic transplantation tumor models. Bufalin was injected intraperitoneally at 1 or 1.5 mg/kg. LY294002 ( ...[more]

PMID: 24581171

Similar Datasets

Project description:BACKGROUND: Hepatocellular carcinoma (HCC) usually has a dismal prognosis because of its limited response to current pharmacotherapy and high metastatic rate. Sulfated oligosaccharide has been confirmed as having potent antitumor activities against solid tumors. Here, we explored the preclinical effects and molecular mechanisms of isomalto oligosaccharide sulfate (IMOS), another novel sulfated oligosaccharide, in HCC cell lines and a xenograft model. METHODS: The effects of IMOS on HCC proliferation, apoptosis, adhesion, migration, and invasiveness in vitro were assessed by cell counting, flow cytometry, adhesion, wound healing, and transwell assays, respectively. The roles of IMOS on HCC growth and metastasis in xenograft models were evaluated by tumor volumes and fluorescent signals. Total and phosphorylated protein levels of AKT, ERK, and JNK as well as total levels of c-MET were detected by Western blotting. IMOS-regulated genes were screened by quantitative reverse-transcription PCR (qRT-PCR) array in HCCLM3-red fluorescent protein (RFP) xenograft tissues and then confirmed by qRT-PCR in HepG2 and Hep3B cells. RESULTS: IMOS markedly inhibited cell proliferation and induced cell apoptosis of HCCLM3, HepG2, and Bel-7402 cells and also significantly suppressed cell adhesion, migration, and invasion of HCCLM3 in vitro. At doses of 60 and 90 mg/kg/d, IMOS displayed robust inhibitory effects on HCC growth and metastasis without obvious side effects in vivo. The levels of pERK, tERK, and pJNK as well as c-MET were significantly down-regulated after treatment with 16 mg/mL IMOS. No obvious changes were found in the levels of pAkt, tAkt, and tJNK. Ten differentially expressed genes were screened from HCCLM3-RFP xenograft tissues after treatment with IMOS at a dose of 90 mg/kg/d. Similar gene expression profiles were confirmed in HepG2 and Hep3B cells after treatment with 16 mg/mL IMOS. CONCLUSIONS: IMOS is a potential anti-HCC candidate through inhibition of ERK and JNK signaling independent of p53 and worth studying further in patients with HCC, especially at advanced stages.

Dataset Information

Bufalin attenuates the stage and metastatic potential of hepatocellular carcinoma in nude mice.

Publications

Bufalin attenuates the stage and metastatic potential of hepatocellular carcinoma in nude mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets