tetrazanbigen and Liver-Neoplasms

TNBG-5602 is a newly synthesized compound with an isoquinoline structure. In the present study, we demonstrated the anticancer effect of TNBG-5602 in in-vitro and in-vivo models and investigated its possible anticancer mechanism.. The antiproliferation effect of TNBG-5602 in vitro was evaluated in human liver cancer cell line QGY-7701. The acute toxicity of TNBG-5602 was evaluated in mice. The anticancer activity of TNBG-5602 in vivo was assessed in a xenograft model of human liver cancer cell line QGY-7701.. Our results suggested that TNBG-5602 might exert potent anticancer activity through increasing the expression of PPARγ.

Topics: Animals; Antineoplastic Agents; Azo Compounds; Cell Line, Tumor; Cell Proliferation; Down-Regulation; Female; Gonanes; Humans; Liver Neoplasms; Male; Mice; Mice, Nude; PPAR gamma; Proliferating Cell Nuclear Antigen; Quinoxalines; Up-Regulation

Tetrazanbigen (TNBG) is a newly synthesized compound with an isoquinoline moiety, and its antitumour effects were evaluated in in-vitro and in-vivo models.. 3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay was used to measure the antiproliferative activity of TNBG on cancer cell lines. Antitumour activity of TNGB in vivo was also assessed in a xenograft model of human hepatocellular carcinoma QGY-7701 cell line. Cell cycle and cell apoptosis analysis was performed.. TNBG exhibited strong antitumour efficacy against six human cancer cell lines with IC50 range of 2.13-8.01 μg/ml. The IC50 of TNBG on normal hepatic cells was 11.25 μg/ml. Lots of lipid droplets were observed in cytoplasm of human hepatocellular carcinoma QGY-7701 cells after treatment of TNBG. S phase arrest and apoptosis induction by TNBG were also found on QGY-7701 cells. Intraperitoneal injection of TNBG (1.5 mg/kg/day) resulted in significant decreases in tumour volume and tumour weight on nude mice bearing QGY-7701 cells xenografts. Results from pathological analysis in nude mice demonstrated that TNBG could induce lipid accumulation specifically in cancer tissue rather than in other normal organs, tissues and blood.. These results suggested that TNBG might exert potent antitumour activity through inducing lipid accumulation in cancer cell.

Topics: Animals; Antineoplastic Agents; Apoptosis; Azo Compounds; Carcinoma, Hepatocellular; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Female; Gonanes; Humans; Inhibitory Concentration 50; Lipids; Liver Neoplasms; Mice; Mice, Nude; Neoplasms; Xenograft Model Antitumor Assays

To investigate the clinical efficacy of cryotherapy ablation treatment for advanced hepatocellular carcinoma, and to analyse the predictive factors of cryotherapy ablation treatment.. 190 patients of hepatitis B-related advanced HCC from 2005 to 2008 in our hospital underwent curative cryoablation. We used clinical cohort method to analyze cryoablation group (147 cases) and control group (43 cases). The median OS (over survival time) and TTP (time to disease progression) were compared. We also evaluated the clinical significance of age, gender, location of portal vein tumor thrombus, HBeAg, tumor histological grade, Child-Pugh classification, end-stage liver disease (MELD) score, advanced liver cancer prediction system (ALCPS) score and the Eastern Cooperative Oncology Group performance status (ECOG PS) score for predicting the efficacy of cryoablation. Two Groups were compared with the x² test. Survival rates were estimated by the Kaplan-Meier method and compared by the log rank test. The Cox proportional hazards model was used to determine the independent factors on survival based on the variables selected in univariate analysis.. Median survival time of cryoablation group and Control group were 7.5 (4.2 to 14.6) months and 3.2 (1.2 to 8.6) months, median TTP were 3.5 (2.5 to 4.5) months and 1.5 (1.0 to 3.5 months), the differences between were statistically significant (P < 0.05). Median OS and TTP of advanced HCC patients who had Well-differentiated tumor, Child-pugh A-class and low score of MELD score, ALCPS score; ECOG PS score were significantly longer than that of the poorly differentiated tumor, Child-pugh B-class and the high those scores (P < 0.05). ECOG PS (P less than 0.05, 95% CI 1.074 - 2.143) and ALCPS (P < 0.05, 95% CI 1.005-2.121) were independent predictors for OS of advanced HCC.. Cryoablation treatment can prolong median OS and TTP of advanced HCC. ECOG PS and ALCPS are important predictors for survival time of advanced HCC.

Topics: Azo Compounds; Carcinoma, Hepatocellular; Cell Line, Tumor; Gonanes; Humans; Liver Neoplasms; Proteomics

Tetrazanbigen (TNBG) is a novel synthetic antitumor drug with significant antitumor effects on common solid tumors in vitro and in vivo. It may lead to death of cancer cells through a tumor-associated lipoidosis mechanism, and result in lipid droplets (LDs) accumulation at the cytoplasm. In this study, the effects of TNBG on protein expression in human hepatocellular carcinoma cell line QGY-7701 were studied for elucidating its antitumor mechanism. The proteins extracted from TNBG-treated human hepatocellular carcinoma cell line QGY-7701 were analyzed and compared with control cells by two-dimensional gel electrophoresis. The differential proteins were identified by matrix-associated laser desorption ionization time-of-flight mass (MALDI-TOF-MS) spectrometry. Two proteins of interest, the levels of which were significantly increased in TNBG-treated cells, were further characterized by Western blot analysis. The results showed a total of 846+/-23 spots in control cells and 853+/-30 spots in TNBG-treated cells. Twenty-six up-regulated or down-regulated proteins were found by analyzing differential proteomic 2-DE map. Eleven of them were identified by mass spectrometry. They were protein disulfide-isomerase precursor, 94 kD glucose-regulated protein, heat shock protein (HSP) 90-alpha, ATP-citrate lyase, HMG-CoA reductase, glucose-6-phosphate 1-dehydrogenase, very-long-chain specific acyl-CoA dehydrogenase, squalene synthetase, sterol regulatory element-binding protein 1, fructose-bisphosphate aldolase A, and peroxiredoxin-1. These up-regulated or down-regulated proteins are mostly related to lipid metabolism. The TNBG antitumor mechanism is probably to influence tumor lipid metabolism, resulting in accumulation of LDs in tumor cells.

Topics: Antineoplastic Agents; Azo Compounds; Carcinoma, Hepatocellular; Cell Line, Tumor; Gonanes; Humans; Liver Neoplasms; Proteins; Proteome