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Pim-2 Activates API-5 to Inhibit the Apoptosis of Hepatocellular Carcinoma Cells Through NF-κB Pathway

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Pathology & Oncology Research

Abstract

Pim-2 is proved to be relevant to the tumorigenesis of hepatocellular carcinoma (HCC), but the mechanism is unclear. We studied the relationship among Pim-2, NF-κB and API-5. In our experiment, expression level of the three factors and phosphorylation level of API-5, as well as NF-κB activity, were detected in HCC tissues and the nontumorous controls. Then Pim-2 gene was transfected into nontumorous liver cells L02, and Pim-2 SiRNA was transfected into hepatoblastoma cell line HepG2. Parthenolide was added as NF-κB inhibitor. The same detections as above were repeated in the cells, along with the apoptosis analysis. We found the levels of Pim-2, NF-κB and API-5, as well as NF-κB activity, were significantly higher in HCC tissues. Pim-2 level was increased in L02 cells after the transfection of Pim-2 gene, but decreased in HepG2 cells after the transfection of Pim-2 SiRNA. The levels of NF-κB and API-5, as well as NF-κB activity and API-5 phosphorylation level, were in accordance with Pim-2 level, but could be reversed by Parthenolide. Cell apoptosis rates were negatively correlated with API-5 phosphorylation level. Therefore, we infer that Pim-2 could activate API-5 to inhibit the apoptosis of liver cells, and NF-κB is the key regulator.

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Abbreviations

Pim:

Proviral integration of Monoley virus

HCC:

hepatocellular carcinoma

NF-κB:

nuclear factor kappa B

Bcl-2:

B-cell CLL/lymphoma 2

Bad:

Bcl2-antagonist of cell death

API-5:

apoptosis inhibitor 5

PNL:

paired noncancerous liver tissues

NL:

normal liver tissues

DEPC:

diethyl pyrocarbonate

SDS-PAGE:

sodium dodecyl sulfate polyacrylamide gel electropheresis

EMSA:

Electrophoretic mobility shift assay

eI4B:

Eukaryotic initiation factor 4B

Myc:

myelocytomatosis

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Acknowledgement

This research is supported by National Natural Scientific Foundation of China (No. 30400424).

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China

    Ke Ren, Wei Zhang & Jianping Gong

  2. West China Hospital of Sichuan University, Chengdu, People’s Republic of China

    Yujun Shi

  3. Department of Hepatobiliary Surgery, The Second College of Clinical Medicine and The Second Affiliated Hospital of Chongqing Medical University, 76# Linjiang Road, Chongqing, 400010, People’s Republic of China

    Jianping Gong

Authors
  1. Ke Ren
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  2. Wei Zhang
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  4. Jianping Gong
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Correspondence to Jianping Gong.

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Ren, K., Zhang, W., Shi, Y. et al. Pim-2 Activates API-5 to Inhibit the Apoptosis of Hepatocellular Carcinoma Cells Through NF-κB Pathway. Pathol. Oncol. Res. 16, 229–237 (2010). https://doi.org/10.1007/s12253-009-9215-4

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  • DOI: https://doi.org/10.1007/s12253-009-9215-4

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