Bid sensitizes apoptosis induced by chemotherapeutic drugs in hepatocellular carcinoma

  • Authors:
    • Ji Miao
    • George G. Chen
    • Suk-Ying Chun
    • Ernest C.W. Chak
    • Paul B.S. Lai
  • View Affiliations

  • Published online on: September 1, 2004     https://doi.org/10.3892/ijo.25.3.651
  • Pages: 651-659
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Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies in Asia. HCC is often resistant to chemotherapy and the mechanism remains unclear. Mitochondrion-mediated pathway is critical in hepatocyte apoptosis, which suggests Bcl-2 family genes may play a role in the regulation of chemotherapy in HCC. In the present study, we investigated the role of BH3 domain-only protein Bid in HCC tissues, HCC-derived cell lines and how the expression of Bid was related to chemotherapeutic agent-induced apoptosis. Bid was differently expressed in HCC tissues and hepatoma cell lines. Hep3B, a Bid-abundant HCC cell line, was more sensitive to drug-induced cytotoxicity than PLC/PRF/5, a Bid-insufficient HCC cell line. The level of caspase activity induced by 5-fluorouracil (5-FU) was higher in Hep3B than in PLC/PRF/5 and a significant increase in the activity occurred at a rather late stage, after 48 h of the treatment. Similar to the activation of caspase, Bid cleavage and activation was only significant at 72 h after the treatment. Overexpression of Bid or tBid sensitized HCC cells to 5-FU and doxorubicin (Dox) treatments. We further demonstrated that such a sensitive effect could be offset by Bcl-xL, as Bid- or tBid-induced apoptosis was completely blocked by the over-expression of Bcl-xL. These results indicate the level of Bid expression is closely associated with the sensitivity of HCC cells to chemotherapeutic drugs, suggesting that Bid plays an important role in HCC management.

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September 2004
Volume 25 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Miao J, Chen GG, Chun S, Chak EC and Lai PB: Bid sensitizes apoptosis induced by chemotherapeutic drugs in hepatocellular carcinoma. Int J Oncol 25: 651-659, 2004.
APA
Miao, J., Chen, G.G., Chun, S., Chak, E.C., & Lai, P.B. (2004). Bid sensitizes apoptosis induced by chemotherapeutic drugs in hepatocellular carcinoma. International Journal of Oncology, 25, 651-659. https://doi.org/10.3892/ijo.25.3.651
MLA
Miao, J., Chen, G. G., Chun, S., Chak, E. C., Lai, P. B."Bid sensitizes apoptosis induced by chemotherapeutic drugs in hepatocellular carcinoma". International Journal of Oncology 25.3 (2004): 651-659.
Chicago
Miao, J., Chen, G. G., Chun, S., Chak, E. C., Lai, P. B."Bid sensitizes apoptosis induced by chemotherapeutic drugs in hepatocellular carcinoma". International Journal of Oncology 25, no. 3 (2004): 651-659. https://doi.org/10.3892/ijo.25.3.651