Suppression of Peroxiredoxin 4 in Glioblastoma Cells Increases Apoptosis and Reduces Tumor Growth

被引：40

作者：

Kim, Tae Hyong ^{[1
,2
]}

Song, Jieun ^{[1
,2
]}

Llaguno, Sheila R. Alcantara ^{[3
]}

Murnan, Eric ^{[1
,2
]}

Liyanarachchi, Sandya ^{[4
]}

Palanichamy, Kamalakannan ^{[5
]}

Yi, Ji-Yeun ^{[1
,2
]}

Viapiano, Mariano Sebastian ^{[1
]}

Nakano, Ichiro ^{[1
]}

Yoon, Sung Ok ^{[6
]}

Wu, Hong ^{[7
,8
]}

Parada, Luis F. ^{[3
]}

Kwon, Chang-Hyuk ^{[1
,2
]}

机构：

[1] Ohio State Univ, Dardinger Ctr Neurooncol & Neurosci, Dept Neurol Surg, Wexner Med Ctr, Columbus, OH 43210 USA

[2] Ohio State Univ, Solid Tumor Program, James Comprehens Canc Ctr, Wexner Med Ctr, Columbus, OH 43210 USA

[3] Univ Texas SW Med Ctr Dallas, Dept Dev Biol, Dallas, TX 75390 USA

[4] Ohio State Univ, Human Canc Genet Program, Wexner Med Ctr, Columbus, OH 43210 USA

[5] Ohio State Univ, Dept Radiat Oncol, Wexner Med Ctr, Columbus, OH 43210 USA

[6] Ohio State Univ, Dept Mol & Cellular Biochem, Wexner Med Ctr, Columbus, OH 43210 USA

[7] Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA USA

[8] Univ Calif Los Angeles, Sch Med, Inst Mol Med, Los Angeles, CA USA

来源：

PLOS ONE | 2012年 / 7卷 / 08期

关键词：

OXIDATIVE STRESS; SIGNAL-TRANSDUCTION; PROTECTS CELLS; GLIOMA-CELLS; P53; EXPRESSION; RADIATION; CANCER; DIFFERENTIATION; PROLIFERATION;

D O I：

10.1371/journal.pone.0042818

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Glioblastoma multiforme (GBM), the most common and aggressive primary brain malignancy, is incurable despite the best combination of current cancer therapies. For the development of more effective therapies, discovery of novel candidate tumor drivers is urgently needed. Here, we report that peroxiredoxin 4 (PRDX4) is a putative tumor driver. PRDX4 levels were highly increased in a majority of human GBMs as well as in a mouse model of GBM. Reducing PRDX4 expression significantly decreased GBM cell growth and radiation resistance in vitro with increased levels of ROS, DNA damage, and apoptosis. In a syngenic orthotopic transplantation model, Prdx4 knockdown limited GBM infiltration and significantly prolonged mouse survival. These data suggest that PRDX4 can be a novel target for GBM therapies in the future.

引用

页数：13

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