Expression level of Bcl-XL critically affects sensitivity of hepatocellular carcinoma cells to LIGHT-enhanced and interferon-γ-induced apoptosis
العنوان: | Expression level of Bcl-XL critically affects sensitivity of hepatocellular carcinoma cells to LIGHT-enhanced and interferon-γ-induced apoptosis |
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المؤلفون: | Dong Wu, Ying Zou, Yi-Zhen Wang, Lixin Wei, Feng Shen, Jun Li, Lehua Shi, Meng-Chao Wu |
المصدر: | Oncology Reports. |
بيانات النشر: | Spandidos Publications, 2007. |
سنة النشر: | 2007 |
مصطلحات موضوعية: | Inhibitor of apoptosis domain, Cancer Research, Programmed cell death, biology, Bcl-xL, General Medicine, Transfection, Oncology, Apoptosis, Cancer research, medicine, biology.protein, Interferon gamma, Signal transduction, Lymphotoxin beta receptor, medicine.drug |
الوصف: | The molecular mechanisms of apoptosis caused by IFN-gamma (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-gamma/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-gamma-mediated apoptosis in Hep3B cells. IFN-gamma/LIGHT-induced apoptosis was inhibited by blocking peptides to the lymphotoxin beta receptor (LT-beta R), and not by the herpes virus entry mediator (HVEM). Expression of LT-beta R remained unchanged after cytokine treatments. IFN-gamma/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-gamma/LIGHT-induced apoptosis. Overexpression of Bcl-XL in Hep3B cells increased the resistance to IFN-gamma/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-gamma/LIGHT- induced apoptosis in HCC cells and may help to select better therapeutic strategies for certain cancers with distinct Bcl-XL expression. |
تدمد: | 1791-2431 1021-335X |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::91dcf29ff21f2e34010dc8f9f990bf8aTest https://doi.org/10.3892/or.17.5.1067Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi...........91dcf29ff21f2e34010dc8f9f990bf8a |
قاعدة البيانات: | OpenAIRE |
تدمد: | 17912431 1021335X |
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