Adenovirus-mediated tBid overexpression results in therapeutic effects on p53-resistant hepatocellular carcinoma
✍ Scribed by Ji Miao; George G. Chen; Suk-Ying Chun; Jing-Ping Yun; Ernest C.W. Chak; Rocky L.K. Ho; Paul B.S. Lai
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- French
- Weight
- 627 KB
- Volume
- 119
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with a very high mortality. Because the success of the conventional therapies is limited, gene therapy may represent an alternative for HCC management. Our earlier study has shown that Bid plays a role in the development of HCC. The aim of our study is to evaluate the possibility of using truncated Bid (tBid) as a novel therapy for HCC treatment. Two HCC cell lines, Hep3B and PLC/PRF/5, were used in the experiment. Hep3B was a p53‐resistant while PLC/PRF/5 a p53‐sensitive. A recombinant adenovirus‐Ad/AFPtBid, which contained a tBid gene driven by an α‐fetoprotein (AFP) promoter, was constructed. Both Hep3B and PLC/PRF/5 cells infected with Ad/AFPtBid showed a significant decrease in cell viability. The decrease in cell viability by Ad/AFPtBid resulted from apoptosis of HCC cells, evident by enhanced activity of caspases and increased release of cytochrome c. In vivo experiment was performed by the intratumor injection of Ad/AFPtBid in nude mice inoculated with Hep3B. Ad/AFPtBid injection significantly inhibited tumor growth, and tumor tissues showed a marked increase in TUNEL‐positive cells. Our experiment also demonstrated that Ad/AFPtBid only targeted AFP‐producing cells but not those non‐AFP producing cells. In conclusion, these results indicate that the introduction of Ad/AFPtBid can not only significantly but specifically kill HCC cells that produce AFP. The cell death induced by Ad/AFPtBid in HCC cells is via an apoptotic pathway that can be independent of p53 status. © 2006 Wiley‐Liss, Inc.