NEW YORK (Reuters Health) - Transfer of a survivin mutant by means of a recombinant adeno-associated virus (rAAV) vector induces apoptosis and inhibits tumor growth in a murine colon cancer model, researchers in China and Canada report in the February issue of Gastroenterology.
As senior investigator Dr. Benjamin C. Y. Wong told Reuters Health, “this study showed that our survivin dominant negative mutant, which is quite specific for cancer - and received a lot of attention as a new cancer target - can be delivered effectively using the rAAV vector in a mouse model, and does not cause harm to normal organs.”
Dr. Wong of the University of Hong Kong and colleagues note that AAV vectors may mediate gene transfer to malignant tumors with “better safety, efficacy and consistency than other available gene delivery methods.”
They further note that survivin is expressed in most common tumors and is involved in carcinogenesis and angiogenesis in colon cancer. It is not expressed in normal adult differentiated tissue.
The researchers found that, in vitro, transduction of colon cancer with the rAAV survivin mutant Cys84Ala inhibited proliferation of colon cancer cells, induced apoptosis and brought about mitotic catastrophe. It also sensitized colon cancer cells to chemotherapeutic drugs.
Intratumoral injection in a mouse xenograft colon cancer model also significantly induced apoptosis and mitotic catastrophe and inhibited tumor growth. Moreover, mutant survivin expression strongly enhanced the anti-tumor activity of 5-FU.
Thus, the researchers, conclude, “targeting the survivin pathway is a novel antiangiogenic and antineoplastic treatment strategy.”
The work, Dr. Wong added, “provides background for human trials - if all the regulations on rAAVs can be sorted out.”
Source: Gastroenterol 2005;128:361-375. [ Google search on this article ]
MeSH Headings:Colonic Diseases: Colonic Neoplasms: Digestive System Neoplasms: DNA, Recombinant: Gastrointestinal Neoplasms: Genetic Techniques: Genetic Vectors: Intestinal Neoplasms: Investigative Techniques: Neoplasms: Neoplasms by Site: Colorectal Neoplasms: Gene Transfer: Analytical, Diagnostic and Therapeutic Techniques and Equipment: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
