Synergistic Suppressive Effect of PARP-1 Inhibitor PJ34 and HDAC Inhibitor SAHA on Proliferation of Liver Cancer Cells  

作　　者：梁宾勇 熊敏 纪桂宝 张二雷 张尊义 董可帅 陈孝平 黄志勇 

机构地区：[1]Research Laboratory and Hepatic Surgery Center,Department of Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology [2]Department of Obstetrics and Gynecology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology [3]Department of General Surgery,Pu’ai Hospital,Tongji Medical College,Huazhong University of Science and Technology

出　　处：《Journal of Huazhong University of Science and Technology(Medical Sciences)》2015年第4期535-540,共6页华中科技大学学报（医学英德文版）

基　　金：supported by grants from the National Natural Science Foundation of China(No.81172293);the New Century Excellent Talent Foundation of Ministry of Education of China(No.NCET-04-0701)

摘　　要：Summary： Poly （ADP-ribose） polymerase-1 （PARP-1） inhibitors and histone deacetylase （HDAC） in- hibitors have recently emerged as promising anticancer drugs. The aim of this study was to investigate the effect of combination treatment with the PARP inhibitor P J34 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 panol/L）, alone or combined, by Cell Counting Kit-8 assay and flow cytometry, respectively. The nude mice bear- ing 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 P J34 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 P J34 or SAHA alone （P〈0.05）. It was led to conclude that P J34 and SAHA can synergistically suppress the proliferation of liver cancer cells.Summary： Poly （ADP-ribose） polymerase-1 （PARP-1） inhibitors and histone deacetylase （HDAC） in- hibitors have recently emerged as promising anticancer drugs. The aim of this study was to investigate the effect of combination treatment with the PARP inhibitor P J34 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 panol/L）, alone or combined, by Cell Counting Kit-8 assay and flow cytometry, respectively. The nude mice bear- ing 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 P J34 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 P J34 or SAHA alone （P〈0.05）. It was led to conclude that P J34 and SAHA can synergistically suppress the proliferation of liver cancer cells.

关 键 词：poly （ADP-ribose） polymerase-1 PJ34 histone deacetylase SAHA liver cancer prolif- eration 

分 类 号：R735.7[医药卫生—肿瘤]