ABSTRACT
Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors and histone deacetylase (HDAC) inhibitors have recently emerged as promising anticancer drugs. The aim of this study was to investigate the effect of combination treatment with the PARP inhibitor PJ34 and HDAC inhibitor SAHA on the proliferation of liver cancer cells. Cell proliferation and apoptosis were assessed in three human liver cancer cell lines (HepG2, Hep3B and HCC-LM3) treated with PJ34 (8 μmol/L) and SAHA (1 μmol/L), alone or combined, by Cell Counting Kit-8 assay and flow cytometry, respectively. The nude mice bearing subcutaneous HepG2 tumors were administered different groups of drugs (10 mg/kg PJ34, 25 mg/kg SAHA, 10 mg/kg PJ34+25 mg/kg SAHA), and the inhibition rates of tumor growth were compared between groups. The results showed that combined use of PJ34 and SAHA could synergistically inhibit the proliferation of liver cancer cell lines HepG2, Hep3B and HCC-LM3. The apoptosis rate of HepG2 cells treated with PJ34+SAHA was significantly higher than that of HepG2 cells treated with PJ34 or SAHA alone (P<0.05). In vivo, the tumor inhibition rates were 53.5%, 61.4% and 82.6% in PJ34, SAHA and PJ34+SAHA groups, respectively. The combined use of PJ34 and SAHA could significantly inhibit the xenograft tumor growth when compared with use of PJ34 or SAHA alone (P<0.05). It was led to conclude that PJ34 and SAHA can synergistically suppress the proliferation of liver cancer cells.
Subject(s)
Animals , Humans , Mice , Antineoplastic Combined Chemotherapy Protocols , Cell Line, Tumor , Cell Proliferation , Drug Synergism , Hep G2 Cells , Histone Deacetylase Inhibitors , Pharmacology , Hydroxamic Acids , Pharmacology , Liver Neoplasms , Drug Therapy , Phenanthrenes , Pharmacology , Poly(ADP-ribose) Polymerase Inhibitors , Pharmacology , Xenograft Model Antitumor AssaysABSTRACT
<p><b>OBJECTIVES</b>To compare the outcomes after liver resection for a single small hepatocellular carcinoma (HCC) (≤ 5 cm) between non-cirrhotic patients and cirrhotic patients, and to explore the influence of liver cirrhosis on recurrence and overall survival after liver resection in patients with a single small HCC.</p><p><b>METHODS</b>A consecutive series of 256 patients with a single small HCC undergoing liver resection from April 2001 to October 2009 was retrospectively reviewed. Among the 256 patients, 227 patients were male, and 29 were female. The medium age was 49 years (ranged, 14 - 79 years); 224 (87.5%) patients were positive for hepatitis B surface antigen, 241 (94.1%) patients were with preoperative liver function of Child-Pugh grade A. The entire cohort were divided into non-cirrhosis group (n = 44) and cirrhosis group (n = 212). Univariate analysis and then multivariate analysis were performed to determine the prognostic factors of recurrence and overall survival after liver resection for all patients.</p><p><b>RESULTS</b>The 1-, 3-, 5-year recurrence-free survival rates after liver resection were 93.0%, 85.3%, and 68.5%, respectively, in non-cirrhosis group, while 81.1%, 58.6%, and 45.0%, respectively, in cirrhosis group. The 1-, 3-, 5-year overall survival rates after liver resection were 100%, 92.5%, and 92.5%, respectively, in non-cirrhosis group, while 93.8%, 78.7%, and 67.8%, respectively, in cirrhosis group. Both the recurrence-free survival and overall survival of non-cirrhosis group were significantly better than those of cirrhosis group (χ(2) = 8.756, P = 0.003; χ(2) = 8.603, P = 0.003). Cirrhosis, absence of tumor capsule, presence of microvascular invasion and moderate/poor tumor differentiation were the independent adverse prognostic factors for recurrence-free survival and overall survival in patients with a single small HCC after liver resection.</p><p><b>CONCLUSIONS</b>Cirrhosis is an important adverse prognostic factor for long-term survival in patients with a single small HCC after liver resection. Liver resection resulted in much worse survival for cirrhotic patients compared to non-cirrhotic patients.</p>