원문정보
초록
영어
Research multi-target-multi-drug approaches need to be accelerated in the view of designing efficient therapeutic strategies against diseases bearing alterations in multiple cellular targets. Expression of untargeted protein leading desired or undesired off-target effects is one of the major
concerns in performing multi-target-multi-drug approaches. In this study, we investigated the possibility of off-target effects of 4-phenylbutyrate and Iressa (Gefitinib) on the expression of vascular endothelial growth factor (VEGF) and histone deacetylase (HDAC), respectively. Treatment with 10 μM Iressa at the time of co-transfection or 48h after co-transfection
of RFP-HDAC/YFP-VEGF plasmids in HEK 293 cells resulted in off-target effects on HDAC protein. These interesting results indicate possible applications of Iressa in the treatment of disease (e.g., Mantle cell lymphoma; MCL) wherein both the HDAC and VEGF protein needs
be inhibited. 4-Phenylbutyrate (2.0 mM) did not show any off-target effects on VEGF protein. The developed techniques based on live/single cellular cotransfection imaging can be employed as a higher accuracy multi-target-multi-drug analysis tool at single cellular level to select
better drug combinations.