Expression level of Bcl-XL critically affects sensitivity of hepatocellular carcinoma cells to LIGHT-enhanced and interferon-γ-induced apoptosis

  • Authors:
    • Jun Li
    • Feng Shen
    • Dong Wu
    • Li-Xin Wei
    • Yi-Zhen Wang
    • Le-Hua Shi
    • Ying Zou
    • Meng-Chao Wu
  • View Affiliations

  • Published online on: May 1, 2007     https://doi.org/10.3892/or.17.5.1067
  • Pages: 1067-1075
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Abstract

The molecular mechanisms of apoptosis caused by IFN-γ (interferon gamma)/LIGHT (lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpes virus entry mediator on T cells) have not been studied in detail. The present study was undertaken to gain insights into the signaling pathways involved in apoptosis induced by IFN-γ/LIGHT in hepatocellular carcinoma (HCC) cell lines. Cell proliferation assay, flow cytometry, Western blotting, gene transfer and RNA interference were used in this study. LIGHT enhanced IFN-γ-mediated apoptosis in Hep3B cells. IFN-γ/LIGHT-induced apoptosis was inhibited by blocking peptides to the lymphotoxin β receptor (LT-β R), and not by the herpes virus entry mediator (HVEM). Expression of LT-β R remained unchanged after cytokine treatments. IFN-γ/LIGHT treatment resulted in the down-regulation of Bcl-XL and the activation of caspase-9 and caspase-3 as well as the decrease of phosphorylation of STAT3. HepG2 and SMMC-7721 cells, which showed high levels of endogenous Bcl-XL, displayed resistance to IFN-γ/LIGHT-induced apoptosis. Overexpression of Bcl-XL in Hep3B cells increased the resistance to IFN-γ/LIGHT induced apoptosis while the down-regulation of Bcl-XL in HepG2 and SMMC-7721 cells by RNA interference decreased the resistance. Our study provides important mechanistic insights into IFN-γ/LIGHT- induced apoptosis in HCC cells and may help to select better therapeutic strategies for certain cancers with distinct Bcl-XL expression.

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May 2007
Volume 17 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Li J, Shen F, Wu D, Wei L, Wang Y, Shi L, Zou Y and Wu M: Expression level of Bcl-XL critically affects sensitivity of hepatocellular carcinoma cells to LIGHT-enhanced and interferon-γ-induced apoptosis. Oncol Rep 17: 1067-1075, 2007.
APA
Li, J., Shen, F., Wu, D., Wei, L., Wang, Y., Shi, L. ... Wu, M. (2007). Expression level of Bcl-XL critically affects sensitivity of hepatocellular carcinoma cells to LIGHT-enhanced and interferon-γ-induced apoptosis. Oncology Reports, 17, 1067-1075. https://doi.org/10.3892/or.17.5.1067
MLA
Li, J., Shen, F., Wu, D., Wei, L., Wang, Y., Shi, L., Zou, Y., Wu, M."Expression level of Bcl-XL critically affects sensitivity of hepatocellular carcinoma cells to LIGHT-enhanced and interferon-γ-induced apoptosis". Oncology Reports 17.5 (2007): 1067-1075.
Chicago
Li, J., Shen, F., Wu, D., Wei, L., Wang, Y., Shi, L., Zou, Y., Wu, M."Expression level of Bcl-XL critically affects sensitivity of hepatocellular carcinoma cells to LIGHT-enhanced and interferon-γ-induced apoptosis". Oncology Reports 17, no. 5 (2007): 1067-1075. https://doi.org/10.3892/or.17.5.1067