Phosphodiesterase 3/4 Inhibitor Zardaverine Exhibits Potent and Selective Antitumor Activity against Hepatocellular Carcinoma Both In Vitro and In Vivo Independently of Phosphodiesterase Inhibition
文献类型：期刊论文
| 作者 | Sun, Liping; Quan, Haitian ; Xie, Chengying; Wang, Lei; Hu, Youhong; Lou, Liguang
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| 刊名 | PLOS ONE
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| 出版日期 | 2014-03-05 |
| 卷号 | 9期号:3 |
| ISSN号 | 1932-6203 |
| DOI | 10.1371/journal.pone.0090627 |
| 文献子类 | Article |
| 英文摘要 | Hepatocellular carcinoma (HCC) is the fifth common malignancy worldwide and the third leading cause of cancer-related death. Targeted therapies for HCC are being extensively developed with the limited success of sorafinib. In the present study, we investigated the potential antitumor activity of zardaverine, a dual-selective phosphodiesterase (PDE) 3/4 inhibitor in HCC cells both in vitro and in vivo. Although all zardaverine, PDE3 inhibitor trequinsin and PDE4 inhibitor rolipram increased intracellular cAMP levels through inhibiting PDE activity, only zardaverine significantly and selectively inhibited the proliferation of certain HCC cells, indicating that the antitumor activity of zardaverine is independent of PDE3/4 inhibition and intracellular cAMP levels. Further studies demonstrated that zardaverine induced G0/G1 phase cell cycle arrest of sensitive HCC cells through dysregulating cell cycle-associated proteins, including Cdk4, Cdk6, Cdk2, Cyclin A, Cyclin E, p21 and Rb. Notably, Rb expression was reversely related to the cell sensitivity to zardaverine. The present findings indicate that zardaverine may have potential as targeted therapies for some HCC, and the likely mechanism of action underlying its selective antitumor activity may be related to its regulation of Rb or Rb-associated signaling in cell cycles. |
| WOS关键词 | CANCER-CELL CYCLES ; NUCLEOTIDE PHOSPHODIESTERASE ; III INHIBITOR ; GROWTH ; APOPTOSIS ; CAMP ; PROLIFERATION ; KINASE ; PATHWAY ; RB |
| 资助项目 | National Natural Science Foundation of China[Y201181042] ; National Natural Science Foundation of China[81273546] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program", China[2013ZX09102008] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program", China[2013ZX09402102-001] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000332479400105 |
| 出版者 | PUBLIC LIBRARY SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277159]  |
| 专题 | 药理学第一研究室 |
| 通讯作者 | Lou, Liguang |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Sun, Liping,Quan, Haitian,Xie, Chengying,et al. Phosphodiesterase 3/4 Inhibitor Zardaverine Exhibits Potent and Selective Antitumor Activity against Hepatocellular Carcinoma Both In Vitro and In Vivo Independently of Phosphodiesterase Inhibition[J]. PLOS ONE,2014,9(3). |
| APA | Sun, Liping,Quan, Haitian,Xie, Chengying,Wang, Lei,Hu, Youhong,&Lou, Liguang.(2014).Phosphodiesterase 3/4 Inhibitor Zardaverine Exhibits Potent and Selective Antitumor Activity against Hepatocellular Carcinoma Both In Vitro and In Vivo Independently of Phosphodiesterase Inhibition.PLOS ONE,9(3). |
| MLA | Sun, Liping,et al."Phosphodiesterase 3/4 Inhibitor Zardaverine Exhibits Potent and Selective Antitumor Activity against Hepatocellular Carcinoma Both In Vitro and In Vivo Independently of Phosphodiesterase Inhibition".PLOS ONE 9.3(2014). |
入库方式： OAI收割
来源：上海药物研究所
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