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Tetrandrine (TET), a bis-benzylisoquinoline alkaloid isolated from the dried root of Hang-Fang-Chi (Stephania tetrandra S. Moore), is well known to possess activities including antioxidant, anti-inflammation, anti-fibrotic and anticancer. It is used clinically to treat hypertension and silicosis. In the present study, the anti-proliferative and apoptotic effects of TET were evaluated on three different hepatoma cell lines, namely Hep G2, PLC/PRF/5 and Hep 3B. Using XTT assay, results showed that the IC₅₀ values of TET were 4.35 μM for Hep G2, 9.44 μM for PLC/PRF/5 and 10.41 μM for Hep 3B cells. The CC₅₀ of TET against BNL-CL.2 mouse normal liver cells was 31.12 μM. Interestingly, TET exhibited a lower IC₅₀ value and better selectivity against Hep G2 and PLC/PRF/5 cells than cisplatin. Microscopic observation study, DNA fragmentation assay and flow cytometric analysis further supported apoptotic effect of TET on both PLC/PRF/5 and Hep 3B cells. The cell cycle of PLC/PRF/5 treated with TET appeared to arrest at G2/M phase in a dose-dependent manner, whereas no effect was noted on the cell cycle of Hep 3B cells. The present study concludes that TET exhibited anti-proliferative effect on Hep G2, PLC/PRF/5 and Hep 3B cells in a dose-dependent manner. TET also possesses a lower IC₅₀ and better SI value than cisplatin against Hep G2 and PLC/PRF/5 cells. The effect of TET on cell cycle progression was found to vary with the type of hepatoma cells, suggesting the genetic make-up of the cells play an important role in the response to drug treatment.

Antrodia camphorata, unique fungal specie, has been used as a folk medicine in Taiwan for many years. The purpose of this study was to compare the extracts from the solid-state culture of A. camphorata co-fermented with Chinese medicinal herb (AC-CF) with two other extracts from fruiting bodies (AC-FB) or solid-state culture (AC-SS), for their anti-tumor effects in human hepatoma HepG2 cells. We measured in vitro cell proliferation, percentage of apoptosis, population distribution of cell cycles, Western blot analysis of multiple drugs resistance-1 (MDR-1), and apoptosis-related proteins in HepG2 cells treated with three different preparations of A. camphorate extracts. Our results showed that AC-CF had better anti-proliferation effect on human hepatoma HepG2 cells than AC-FB or AC-SS dose-dependently. In addition, AC-CF in combination with anti-tumor agents (mitomycin C or methotrexate) showed better adjuvant anti-tumor effects than AC-FB or AC-SS. We further demonstrated the augmented adjuvant anti-tumor effects of AC-CF not only through down regulation of MDR-1 expression but also through a COX-2 dependent apoptosis pathway, involving down-regulation of COX-2 and p-AKT and up-regulation of PARP-1. In conclusion, in this study, we have demonstrated a novel strategy of fermenting A. camphorata with Chinese medicinal herb (AC-CF), which augmented their anti-tumor effects in human hepatoma HepG2 cells as compared to the traditional ones (AC-FB or AC-SS).

High mortality and morbidity rates for hepatocellular carcinoma (HCC) in Taiwan primarily result from uncontrolled tumor metastasis. In our previous studies, we have reported that Dioscorea nipponica Makino extract (DNE) has anti-metastasis effects on human oral cancer cells. However, the effect of DNE on hepatoma metastasis have not been thoroughly investigated and remains poorly understood. To determine the effects of DNE on the migration and invasion in HCC cells we used a wound healing model, Boyden chamber assays, gelatin/casein zymography and Western blotting. Transcriptional levels of matrix metalloproteinase-9 (MMP-9) and urokinase-type plasminogen activator (u-PA) were detected by real-time PCR and promoter assays. In this study, DNE treatment significantly inhibited the migration/invasion capacities of Huh7 cell lines. The results of gelatin/casein zymography and Western blotting revealed that the activities and protein levels of the MMP-9 and u-PA were inhibited by DNE. Tests of the mRNA levels, real-time PCR, and promoter assays evaluated the inhibitory effects of DNE on u-PA expression in human hepatoma cells. A chromatin immunoprecipitation (ChIP) assay showed not only that DNE inhibits u-PA expression, but also the inhibitory effects were associated with the down-regulation of the transcription factors of NF-$\kappa$B and SP-1 signaling pathways. Western blot analysis also showed that DNE inhibits PI3K and phosphorylation of Akt. In conclusion, these results show that u-PA expression may be a potent therapeutic target in the DNE-mediated suppression of HCC invasion/migration. DNE may have potential use as a chemo-preventive agent against liver cancer metastasis.

Cinobufagin is a Na⁺/K⁺-ATPase (NKA) inhibitor with excellent anticancer effects to prolong the survival of patients. The purpose of the present study was to clarify the underlying mechanism of the anticancer effects of cinobufagin using overexpression or inhibition of aurora kinase A (AURKA) signaling. First, high expression of Na⁺/K⁺-ATPase alpha 1 subunit (ATP1A1) and AURAK resulted in increased malignant transformation in hepatocellular carcinoma (HCC) patients using the cancer genome atlas (TCGA) data and tissue samples. After treatment with cinobufagin, we successfully screened 202, 249, and 335 changing expression proteins in Huh-7 cells under normal, overexpression, and inhibition of AURKA using tandem mass tags (TMT)-labeled quantitative proteomics coupled to 2D liquid chromatography-tandem mass spectrometry (LC-MS/MS). Bioinformatics analysis revealed that these molecules were closely associated with chromosome segregation, DNA damage, and regulation of translation processes. We further confirmed that cinobufagin induced DNA damage and chromosome segregation disorders and suppresses translational processing in oncogenes by decreasing the expression of AURKA, mechanistic target of rapamycin kinase (mTOR), p-mTOR, p-extracellular regulated protein kinases (ERK), eukaryotic translation initiation factor 4E (eIF4E), and p-eIF4E, while increasing the expression of p-eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) (S65, T37, T46, T45) and increasing the interaction between eIF4 and 4E-BP1. Our results suggested that cinobufagin performed an antitumor effects in liver cancer cells by inhibiting the AURKA-mTOR-eIF4E axis.

In this work, we synthesized lactobionic acid-decorated diselenide-linked polyethylene glycol-doxorubicin conjugate (LA-PEG-SeSe-DOX) and prepared free DOX-loaded LA-PEG-SeSe-DOX(DOX@LA-PEG-SeSe-DOX) nanoparticles for hepatoma-targeted DOX delivery. LA-PEG-SeSe-DOX can self-assemble into nanoparticles in deionized water and DOX@LA-PEG-SeSe-DOX nanoparticles were prepared by loading free DOX into LA-PEG-Se-Se-DOX nanoparticles under sonication. DOX@LA-PEG-SeSe-DOX nanoparticles have high DOX loading content of 31.3%. The dynamic scattering analysis shows that DOX@LA-PEG-SeSe-DOX nanoparticles have small size (hydrodynamic diameter $45.69\pm 0.71$nm), near neutral zeta potential, and excellent colloidal stability. The in vitro drug release study indicates that DOX@LA-PEG-SeSe-DOX nanoparticles exhibit dual redox-responsive drug release characteristics. The cellular uptake study reveals that DOX@LA-PEG-SeSe-DOX nanoparticles can be taken up by hepatoma cells by asialoglycoprotein receptor (ASGPR)-mediated pathway. Finally, DOX@LA-PEG-SeSe-DOX nanoparticles exhibit enhanced cytotoxicity against HepG2 cells as compared to LA-PEG-SeSe-DOX nanoparticles, underlining the significance of releasing free DOX for effective tumor cell proliferation inhibition. This work provides a facile and effective strategy for targeted delivery of DOX to hepatoma cells.

Hepatocellular carcinoma (HCC) is one of the most aggressive abdominal tumors and has a poor prognosis if left untreated. Surgical resection for HCC remains the only potential for cure. Advances in tumor imaging, surgical technique and perioperative care have paved the way for better outcomes following surgical resection of HCC. Mortality rates of less than 5% and long-term survival are achievable by most specialized hepatobiliary units. Moreover, surgeons have now expanded the indications of surgery for HCC to include lesions once considered "irresectable." In this review, we focus on the current status in preoperative selection and optimization of patients, advances in surgical technique as well as the expanding indications of surgery for HCC.

This study proposes a diagnosis system for liver masses based on the improved radial basis function (RBF) neural networks. In this article, RBF networks are improved by sigmoid function and the growing and pruning algorithm. The proposed improved RBF networks adopt the sigmoid function as their kernel due to its increased flexibility over the Gaussian kernel. Furthermore, the growing and pruning algorithm is used to adjust the network size dynamically according to the neuron's significance. This investigation formulates discriminating among cysts, hepatoma, cavernous hemangioma, and normal tissue as a supervised learning problem. The current work calculates several texture and gray-level features derived from regions of interest as input in the proposed classifier. Receiver operating characteristic (ROC) curves evaluate the diagnosis performance, and demonstrate the proposed method's good performance.

The distribution of responses to hepatitis B virus infection in the rural community of Tip, Senegal, has been determined. Children are rarely persistently infected before two years of age, at which time about 25% of the population are infected. Uninfected members continue to be at risk. Vaccination programs instituted at an early age could prevent infection in most of the population and considerably decrease the risk of chronic liver disease and primary cancer of the liver in adults.