PJ34, an inhibitor of PARP-1, suppresses cell growth and enhances the suppressive effects of cisplatin in liver cancer cells
PJ34, an inhibitor of PARP-1, suppresses cell growth and enhances the suppressive effects of cisplatin in liver cancer cells
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PJ34是PARP-1的抑制剂，抑制细胞生长并增强顺铂对肝癌细胞的抑制作用
DOI：
10.3892/or_00000043
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发表时间：
2008-09-01
期刊：
影响因子：
4.2
通讯作者：
Huang, Zhi-Yong
中科院分区：
文献类型：
--
作者：
Huang, Sheng-Hui;Xiong, Min;Huang, Zhi-Yong
研究表明，聚（ADP-核糖）聚合酶-1（PARP-1）在DNA修复、细胞死亡和增殖以及基因组稳定中起重要作用。PARP-1的药理学抑制或基因消融在癌症化疗中具有有益的结果，因为癌细胞缺乏PARP-1并且对化疗DNA损伤敏感。PJ 34作为一种新型的PARP-1特异性抑制剂，已被报道在某些类型的肿瘤中增强化疗效果。在先前的研究中，我们发现PARP-1在人肝细胞癌（HCC）中的表达与其周围肝组织相比显著增加。本研究调查了PJ 34对PARP-1活性的抑制是否对人肝癌细胞产生抑制作用并使肿瘤细胞对化疗剂敏感。我们的结论是，PJ 34显着抑制HepG 2细胞生长的剂量依赖性的方式，并抑制HepG 2细胞来源的裸鼠肿瘤的生长。PJ 34的抑制作用与增加的细胞凋亡有关。此外，PJ 34增强顺铂在HepG 2细胞中的抑制作用。这些结果表明，PJ 34可能被开发成一种有效的药物，用于治疗人类肝癌。
It has been suggested that poly(ADP-ribose) polymerase-1 (PARP-1) plays an important role in DNA repair, cell death and proliferation, as well as in the stabilization of the genome. Pharmacological inhibition or genetic ablation of PARP-1 had a beneficial outcome in cancer chemotherapy since the cancer cells lacked PARP-1 and were sensitive to chemotherapeutic DNA damage. As a novel potent specific inhibitor of PARP-1, PJ34 has been reported to enhance chemotherapeutic effects in certain types of tumors. In a previous study, we found that PARP-1 expression was significantly increased in human hepatocellular carcinoma (HCC) compared to its surrounding liver tissue. This study investigated whether or not the inhibition of PARP-1 activity by PJ34 produces suppressive effects on human liver cancer cells and sensitizes the tumor cells to chemotherapeutic agents. We conclude that PJ34 significantly suppresses HepG2 cell growth in a dose-dependent manner, and inhibits HepG2 cell-derived tumor growth in nude mice. The suppressive effects of PJ34 are associated with increased cell apoptosis. Furthermore, PJ34 enhances suppressive effects of cisplatin in HepG2 cells. These results suggest that PJ34 may be developed into an effective agent for the treatment of human HCC.