Tanshinone IIA Increases the Bystander Effect of Herpes Simplex Virus Thymidine Kinase/Ganciclovir Gene Therapy via Enhanced Gap Junctional Intercellular Communication

摘要: The bystander effect is an intriguing phenomenon by which adjacent cells become sensitized to drug treatment during gene therapy with herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV). This reported be mediated gap junctional intercellular communication (GJIC), and therefore, we postulated that upregulation of genes facilitate GJIC may enhance the HSV-tk/GCV effect. Previous findings have shown Tanshinone IIA (Tan IIA), a chemical substance derived from Chinese medicine herb, promotes connexins Cx26 Cx43 in B16 cells. Because junctions are formed connexins, hypothesized Tan might increase GJIC. Our results show increased melanoma cells, leading more efficient GCV-induced killing stably expressing HSV-tk. Additionally, vivo experiments demonstrated tumors mice 10% HSV-tk positive 90% wild-type became smaller following combination GCV as compared or alone. These data demonstrate can augment system through junction coupling, adds strength promising strategy develops inducer potentiate effects suicide therapy.