BackgroundHepatocellular carcinoma (HCC) is a common and aggressive cancer, and the treatment options are limited for patients with advanced HCC. Bufalin, the major digoxin-like component of the traditional Chinese medicine Chansu, exhibits significant anti-tumor activities in many tumor cell lines. In the present study, we investigated the effect of bufalin on the inhibition of an AKT-related signaling pathway, and examined the relationship between regulatory proteins and anti-tumor effects in hepatoma cells.MethodsProliferation, wound healing, transwell-migration/invasion and adhesion assays were performed in HCCLM3 and HepG2 cell lines. The protein levels of pAKT, AKT, pGSK3β, GSK3β, pβ-catenin, β-catenin, E-cadherin, MMP-9, and MMP-2 were measured by western blot analysis. E-Cadherin and β-catenin expression levels were also evaluated by immunofluorescence.ResultsBufalin inhibited hepatoma cell proliferation, migration, invasion and adhesion. In addition, treatment with bufalin significantly decreased the levels of pAKT, pGSK3β, MMP-9, and MMP-2, while increasing the levels of GSK3β and E-cadherin and suppressing the nuclear translocation of β-catenin.ConclusionsBufalin is a potential anti-HCC therapeutic candidate through its inhibition of the AKT/GSK3β/β-catenin/E-cadherin signaling pathway. Further studies with bufalin are warranted in patients with HCC, especially those with the disease at advanced stages.

BackgroundAdvanced 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.MethodIn 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/GSK3β/β-catenin/E-cadherin signaling pathway-related proteins was detected by immunohistochemistry (IHC) and western blot analysis.ResultsThese 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/GSK3β/β-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.ConclusionBased 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/GSK3β/β-catenin/E-cadherin signaling pathways by bufalin may show therapeutic effects in advanced HCC patients.

Objective: Lung cancer is often associated with hypercoagulability. Thromboelastography provides integrated information on clot formation in whole blood. This study explored the possible relationship between thromboelastography and lung cancer. Methods: Lung cancer was staged according to the Tumor, Node, and Metastasis (TNM) classification system. Thromboelastography parameters in different stages of disease were compared. The value of thromboelastography for stage prediction was determined by area under the receiver operating characteristic curve analysis. Results: A total of 182 patients diagnosed with lung cancer were included. Thromboelastography parameters, including kinetics time, α-angle, and maximum amplitude, differed significantly between patients with metastatic and limited lung cancers ( P < 0.05). Kinetics time was significantly reduced and maximum amplitude was significantly increased in patients with stage I and II compared with stage III and IV tumors ( P < 0.05). TNM stage was significantly negatively correlated with kinetics time ( r = −0.186), and significantly positively correlated with α-angle ( r = 0.151) and maximum amplitude ( r = 0.251) (both P < 0.05). The area under the curve for kinetics time in patients with stage I cancer was 0.637 ( P < 0.05) and that for α-angle in stage ≥ II was 0.623 ( P < 0.05). The areas under the curves for maximum amplitude in stage ≥ III and stage IV cancer were 0.650 and 0.605, respectively (both P < 0.05). Thromboelastography parameters were more closely associated with TNM stage in patients with lung adenocarcinoma than in the whole lung cancer population. Conclusion: This study identified the diagnostic value of thromboelastography parameters for determining tumor stage in patients with lung cancer. Thromboelastography can be used as an independent predictive parameter for lung cancer severity.