Adenovirus-Mediated Vascular Targeting Suicide Gene Therapy in vitro / 中国肿瘤生物治疗杂志

To investigate the potential use of suicide gene systems in vascular targeting gene therapy, HSV-tk/GCV and EC-cd/5-FC systems were established on vascular endothelial cells in vitro by adenovirus transduction. Both modified cell lines were highly sensitive to prodrugs, the IC_(50) for GCV was 0.2?mol/L in IGll/Ad-tk cells, and IC_(50) for 5-FC was 20?mol/L in IGll/Ad-cd cells, while the parental endothelial cells were insensitive even at the highest concentrations of prodrugs in the experiment. Mixed cellular assay showed that significant bystander killing effect was exhibited in modified endothelial cells. Also, the apoptosis involved in these prodrug-mediated growth inhibitions has been shown under electron microscopy. These results indicated that both HSV-tk/GCV and EC-cd/5-FC systems could efficiently suppress vascular endothelial cell growth in vitro , suggesting the feasibility of using suicide gene in vascular targeting gene therapy.

The relationship of gap junction with the bystander effect in the HSV-TK/GCV treatment / 中国药理学通报

The bystander effect(BE) plays an important role in the gene therapy of cancer by the herpes thymidine kinase/ganciclovir(HSV-TK/GCV) system.It enhances the therapeutic efficacy of this system.Up to now,the exact underlying mechanism of the bystander effect remains unclear.A large body of evidence has indicated a close correlation of the connexin expression and gap junction in the targeted cells to the bystander effect.Here the publications concerning the relationship of gap junction with the bystander effect in the HSV-TK/GCV treatment have been reviewed.The possible cell death signals that can be transferred through gap junction to induce the bystander effect are also discussed.