Oncotarget

Research Papers:

SAHA and/or MG132 reverse the aggressive phenotypes of glioma cells: An in vitro and vivo study

Xue-feng Yang, Zhi-juan Zhao, Jia-jie Liu, Xiang-hong Yang, Yang Gao, Shuang Zhao, Shuai Shi and Ke-qiang Huang _

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Oncotarget. 2017; 8:3156-3169. https://doi.org/10.18632/oncotarget.13680

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Abstract

Xue-feng Yang1, Zhi-juan Zhao1, Jia-jie Liu1, Xiang-hong Yang2, Yang Gao1, Shuang Zhao1, Shuai Shi1, Ke-qiang Huang3, Hua-chuan Zheng1,4

1Cancer Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China

2Department of Pathology, Shengjing Hospital of China Medical University, Shenyang 110004, China

3Department of Stomatology, The Second Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China

4Life Science Institute of Jinzhou Medical University, Jinzhou 121001, China

Correspondence to:

Hua-chuan Zheng, email: [email protected]

Keywords: glioma, suberoylanilide hydroxamic acid, histone acetylation, MG132, chemotherapy

Received: August 23, 2016     Accepted: November 15, 2016     Published: November 29, 2016

ABSTRACT

To elucidate the anti-tumor effects and molecular mechanisms of SAHA (a histone deacetylase inhibitor) and MG132 (a proteasome inhibitor) on the aggressive phenotypes of glioma cells, we treated U87 and U251 cells with SAHA or/and MG132, and detected phenotypes’ assays with phenotype-related molecules examined. It was found that SAHA or/and MG132 treatment suppressed proliferation in both concentration- and time-dependent manners, inhibited energy metabolism, migration, invasion and lamellipodia formation, and induced G2 arrest and apoptosis in the glioma cells. The treatment with SAHA increased the expression of acetyl-histones 3 and 4, which were recruited to the promoters of p21, p27, Cyclin D1, c-myc and Nanog to down-regulate their transcriptional levels. Expression of acetyl-histones 3 and 4 was higher in gliomas than normal brain tissues. Both drugs’ exposure suppressed tumor growth in nude mice by inducing apoptosis and inhibiting proliferation, but increased serum aminotransferase and creatinine. These results indicated that SAHA and/or MG132 may suppress the aggressive phenotypes of glioma cells. They might be employed to treat the glioma if both hepatic and renal injuries are prevented.


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