Suppression of cancer growth by nonviral gene therapy based on a novel reactive oxygen species-responsive promoter.

LUCÍA L POLICASTRO, IRENE L IBAÑEZ, HEBE A DURÁN, GASTON SORIA, VANESA GOTTIFREDI, AND OSVALDO L PODHAJCER

NATURE PUBLISHING GROUP

Año: 2009 vol. 17 p. 1355 - 1355

ncreased reactive oxygen species (ROS) production has been reported as a distinctive feature of different pathol- ogies including cancer. Therefore, we assessed whether increased ROS production in the cancer microenviron- ment could be selectively exploited to develop a selec- tive anticancer therapy. For this purpose, we constructed a novel chimeric promoter, based on a ROS-response motif located in the VEGF gene promoter placed, in turn, downstream of a second ROS-response motif obtained from the early growth response 1 (Egr-1) gene promoter. The activity of the chimeric promoter was largely depen- dent on variations in intracellular ROS levels and showed a high inducible response to exogenous H2O2. Transient expression of the thymidine kinase (TK) gene driven by the chimeric promoter, followed by gancyclovir (GCV) administration, inhibited human colorectal cancer and melanoma cell growth in vitro and in vivo. Moreover, electrotransfer of the TK gene followed by GCV adminis- tration