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Treatment With Hydroxyurea and tyrphostin-1 Significantly Improves the Transduction Efficiency of Recombinant Adeno-Associated Viruses in Human Cancer Cells

Sung Jin Kim, Young Ran Nam, Ohkyu Shin, Jene Choi, Boyoung Lee, Jin Woo Chang, Yunhee Kim Kwon, Keerang Park, Heuiran Lee

Oncol Rep. 2005 Dec;14(6):1475-9.

PMID: 16273241

Abstract:

To enhance the transduction efficiency (TE) of a recombinant adeno-associated virus 2 (rAAV2) in human cancer cells, we examined the combined effects of various chemicals known to influence the rAAV2 transduction process at distinct steps. Among the agents tested were trichostatin A, a histone deacetylase inhibitor, MG-132, a proteosome inhibitor, the genotoxic agents hydroxyurea, aphidicolin, etoposide and camptothecin, and tyrphostin-1, an epidermal growth factor receptor inhibitor. During or after chemical treatment, various human cancer cells were infected with rAAV2 expressing beta-galactosidase. Treatment with hydroxy-urea or etoposide plus tyrphostin-1 dramatically increased the TE in most cell lines. The combination of hydroxyurea plus tyrphostin-1 increased TE to 37.7+/-7.9%, 32.8+/-2.0% and 31.8+/-2.1% in SK-Hep1, HeLa, and HCT116 cells, respectively. In addition, following rAAV2 infection and treatment with hydroxyurea plus tyrphostin-1, long-term transgene expression was observed for up to 6 months, with no damage to the transduced cells. These results indicate that rAAV2 transgene expression can be significantly enhanced by a combination of chemical agents with distinct activity and prolonged gene expression can occur following rAAV2 gene transfer into human cancer cells.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP2826268 Tyrphostin 1 Tyrphostin 1 2826-26-8 Price
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