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Tumor Biology

, Volume 34, Issue 6, pp 3397–3405 | Cite as

Abnormal expression of insulin-like growth factor-I receptor in hepatoma tissue and its inhibition to promote apoptosis of tumor cells

  • Zhizhen Dong
  • Min Yao
  • Li Wang
  • Xiaodi Yan
  • Xing Gu
  • Yun Shi
  • Ninghua Yao
  • Liwei Qiu
  • Wei Wu
  • Dengfu Yao
Research Article

Abstract

Abnormal signaling of insulin-like growth factor I receptor (IGF-IR) is associated with hepatocellular carcinoma, but the underlying molecular mechanisms remain largely unknown. The objective of this study was to investigate IGF-IR’s role as a signaling molecule, its pathological alteration in hepatoma tissues, and its effect on hepatoma cell proliferation when inhibited. As measured by immunohistochemical analysis, the incidence of hepatic IGF-IR expression in cancerous tissue was 80.0 % (24 of 30), which was significantly higher (P < 0.05) than 43.3 % (13 of 30) occurrence in the surrounding tissue and the nondetectable (0 of 30) frequency in the distal cancerous tissue. Hepatoma IGF-IR expression was correlated to the differentiation degree and not to the number or size of tumors, HBV infection, and AFP level. The in vitro IGF-IR expression in hepatoma cells was down-regulated significantly by picropodophyllin, a specific kinase inhibitor, in a time- and dose-dependent manner. Cell proliferation was inhibited through typical mechanisms of promoting apoptosis and cell cycle arrest (G2/M phase). Up-regulation of IGF-IR in hepatocarcinogenesis suggests that the down-regulation of IGF-IR expression could be a specific molecular target for hepatoma cell proliferation.

Keyword

Hepatocellular carcinoma Insulin-like growth factor I receptor Molecular target Gene amplification Sequencing Proliferation inhibition Apoptosis 

Abbreviations

2-FAA

2-Fluorenylacetamide

HBV

Hepatitis B virus

HCC

Hepatocellular carcinoma

HCV

Hepatitis C virus

IGF

Insulin-like growth factor

IGF-II

Insulin-like growth factor-II

IGF-IR

Insulin-like growth factor I receptor

PPP

Picropodophyllin

SDS

Sodium dodecyl sulfate

Notes

Acknowledgments

This work was supported by grants-in-aid from some Projects of the Society Development (HS2012039) of Nantong, the Jiangsu Health Projects (BL2012053, K201102), the Priority Academic Program Development of Jiangsu (PADA), and the International S&T Cooperation Program of China (2013DFA32150).

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Zhizhen Dong
    • 1
  • Min Yao
    • 2
  • Li Wang
    • 2
  • Xiaodi Yan
    • 4
  • Xing Gu
    • 4
  • Yun Shi
    • 4
  • Ninghua Yao
    • 4
  • Liwei Qiu
    • 3
  • Wei Wu
    • 3
  • Dengfu Yao
    • 3
  1. 1.Department of DiagnosticsAffiliated Hospital of Nantong UniversityNantongChina
  2. 2.Medical School of Nantong UniversityNantongChina
  3. 3.Research Center of Clinical MedicineAffiliated Hospital of Nantong UniversityNantongChina
  4. 4.Department of OncologyAffiliated Hospital of Nantong UniversityNantongChina

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