Multinucleation regulated by the Akt/PTEN signaling pathway is a survival strategy for HepG2 cells

被引:12
|
作者
Mukherjee, Ananda [1 ]
Misra, Sandip [1 ]
Howlett, Niall G. [2 ]
Karmakar, Parimal [1 ]
机构
[1] Jadavpur Univ, Dept Life Sci & Biotechnol, Kolkata 700032, W Bengal, India
[2] Univ Rhode Isl, Dept Cell & Mol Biol, Kingston, RI 02881 USA
关键词
Chang Liver; Cytokinesis-block micronucleus assay; HepG2; Multinucleation; Akt; PTEN; DNA-DAMAGE; TUMOR-SUPPRESSOR; PTEN; ETOPOSIDE; ACTIVATION; INSTABILITY; DEFICIENT; DIVISION; ARREST; REPAIR;
D O I
10.1016/j.mrgentox.2013.06.009
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Hepatocellular carcinoma (HCC) is non-responsive to many chemotherapeutic agents including etoposide. The aim of this study was to examine the survival strategy of the HCC cell line HepG2 after etoposide treatment. Here we analyzed and compared spontaneous and etoposide-induced DNA damage in HepG2 (a-fetoprotein (AFP)-positive) and Chang Liver (AFP-negative) cell lines. Compared to Chang Liver cells, HepG2 cells exhibited a significantly higher degree of micronucleation and a higher nuclear division index, as determined by the cytokinesis-block micronucleus assay, following exposure to etoposide. HepG2 cells were also more resistant to etoposide-induced cytotoxicity compared to Chang Liver cells. We also establish that increased etoposide-induced multinucleation in HepG2 cells is dependent on the catalytic activity of Akt, as phosphatidylinositol-3-kinase inhibitors as well as the overexpression of kinase-defective Akt reversed this phenotype. Moreover, ectopic expression of wild type PTEN reduced the frequency of etoposide-induced multinucleated HepG2 cells, and restored HepG2 etoposide sensitivity. Taken together, these results implicate the Akt/PTEN cellular axis as a major determinant of the etoposide resistance of HCC cells. (C) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:135 / 140
页数:6
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