Antitumour effects of a protease inhibitor, nelfinavir, in hepatocellular carcinoma cancer cells

被引:14
作者
Sun, Lihua [1 ]
Niu, Lidan [2 ]
Zhu, Xiuying [2 ]
Hao, Jie [1 ]
Wang, Ping [3 ]
Wang, Hongwei [1 ]
机构
[1] Xinxiang Med Univ, Affiliated Hosp 1, Dept Infect Dis, Xinxiang, Henan, Peoples R China
[2] Xinxiang Med Univ, Affiliated Hosp 1, Dept Emergency, Xinxiang, Henan, Peoples R China
[3] Xinxiang Med Univ, Affiliated Hosp 1, Dept Intervent Med, Xinxiang, Henan, Peoples R China
关键词
Nelfinavir; Hepatocellular carcinoma; Non-AIDS-defining malignancies; HIV-INFECTED PATIENTS; ENDOPLASMIC-RETICULUM STRESS; KAPOSI-SARCOMA; CYCLE ARREST; IN-VITRO; APOPTOSIS; IMMUNODEFICIENCY; RITONAVIR; VIRUS; COHORT;
D O I
10.1179/1973947812Y.0000000011
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Nelfinavir is a protease inhibitor with potential antitumour activity against certain cancer types. The objective of this study was to evaluate the antitumour effects of nelfinavir in hepatocellular carcinoma cell lines, Hep G2 and WCH-17. Results indicate that nelfinavir inhibited the proliferation of Hep G2 and WCH-17 cell lines, with IC50 of 5.1 and 62.0 mu mol/l, respectively. Nelfinavir induced apoptosis in both cell lines, although the extent as indicated by Annexin V staining varied. The concentration of nelfinavir needed to induce apoptosis in liver cancer cells were 10 and 100 mu mol/l for HepG2 and WCH-17, respectively. At the same concentrations, nelfinavir induced cell cycle arrest at G0/G1 phase in HepG2 and WCH-17 cell lines. Our results suggest that nelfinavir inhibit hepatoma cell growth, through the induction of apoptosis and cell cycle arrest. However, the clinical relevance of these findings warrants further investigation.
引用
收藏
页码:161 / 166
页数:6
相关论文
共 23 条
[1]   Pharmacokinetics, food intake requirements and tolerability of once-daily combinations of nelfinavir and low-dose ritonavir in healthy volunteers [J].
Aarnoutse, RE ;
Droste, JAH ;
van Oosterhout, JJG ;
Koopmans, PP ;
Popescu, M ;
Reiss, P ;
Hekster, YA ;
Burger, DM .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2003, 55 (02) :115-125
[2]   An updated systematic overview of triple combination therapy in antiretroviral-naive HIV-infected adults [J].
Bartlett, John A. ;
Fath, Michael J. ;
DeMasi, Ralph ;
Hermes, Ashwaq ;
Quinn, Joseph ;
Mondou, Elsa ;
Rousseau, Franck .
AIDS, 2006, 20 (16) :2051-2064
[3]   Presentation and outcome of hepatocellular carcinoma in HIV-infected patients:: A US-Canadian multicenter study [J].
Braeu, Norbert ;
Fox, Rena K. ;
Xiao, Peiying ;
Marks, Kristen ;
Naqvi, Zeenat ;
Taylor, Lynn E. ;
Trikha, Anita ;
Sherman, Morris ;
Sulkowski, Mark S. ;
Dieterich, Douglas T. ;
Rigsby, Michael O. ;
Wright, Teresa L. ;
Hernandez, Maria D. ;
Jain, Mamta K. ;
Khatri, Gajendra K. ;
Sterling, Richard K. ;
Bonacini, Maurizio ;
Martyn, Catherine A. ;
Aytaman, Ayse ;
Llovet, Josep M. ;
Brown, Sheldon T. ;
Bini, Edmund J. .
JOURNAL OF HEPATOLOGY, 2007, 47 (04) :527-537
[4]   Nelfinavir induces liposarcoma apoptosis and cell cycle arrest by upregulating sterol regulatory element binding protein-1 [J].
Chow, Warren A. ;
Guo, Song ;
Valdes-Albini, Frances .
ANTI-CANCER DRUGS, 2006, 17 (08) :891-903
[5]   Influence of HIV-related immunodeficiency on the risk of hepatocellular carcinoma [J].
Clifford, Gary M. ;
Rickenbach, Martin ;
Polesel, Jerry ;
Dal Maso, Luigino ;
Steffen, Ingrid ;
Ledergerber, Bruno ;
Rauch, Andri ;
Probst-Hensch, Nicole M. ;
Bouchardy, Christine ;
Levi, Fabio ;
Franceschi, Silvia .
AIDS, 2008, 22 (16) :2135-2141
[6]   The Impact of Nelfinavir Exposure on Cancer Development Among a Large Cohort of HIV-Infected Patients [J].
Crum-Cianflone, Nancy E. ;
Hullsiek, Katherine Huppler ;
Marconi, Vincent ;
Weintrob, Amy ;
Ganesan, Anuradha ;
Barthel, R. Vincent ;
Fraser, Susan ;
Roediger, Mollie Poehlnian ;
Agan, Brian ;
Regner, Scott .
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2009, 51 (03) :305-309
[7]  
Gaedicke S, 2002, CANCER RES, V62, P6901
[8]   Nelfinavir, a lead HIV protease inhibitor, is a broad-spectrum, anticancer agent that induces endoplasmic reticulum stress, autophagy, and apoptosis in vitro and in vivo [J].
Gills, JoellJ. ;
Lo Piccolo, Jaclyn ;
Tsurutani, Junji ;
Shoemaker, Robert H. ;
Best, Carolyn J. M. ;
Abu-Asab, Mones S. ;
Borojerdi, Jennifer ;
Warfel, Noel A. ;
Gardner, Erin R. ;
Danish, Matthew ;
Hollander, M. Christine ;
Kawabata, Shigeru ;
Tsokos, Maria ;
Figga, William D. ;
Steeg, Patricia S. ;
Dennis, Phillip A. .
CLINICAL CANCER RESEARCH, 2007, 13 (17) :5183-5194
[9]   Cirrhosis and hepatocellular carcinoma in HIV-infected veterans with and without the hepatitis C virus - A cohort study, 1992-2001 [J].
Giordano, TP ;
Kramer, JR ;
Souchek, J ;
Richardson, P ;
El-Serag, HB .
ARCHIVES OF INTERNAL MEDICINE, 2004, 164 (21) :2349-2354
[10]  
Herida M, J CLIN ONCOL, V21, P3447