Role of GJIC on the Bystander Effect Mediated by HSV-TK/GCV Approach and Its Regulation

Abstract: Reinforcement of the so-called " bystander effect" is a key way to improve the efficacy of HSV-TK/GCV approach. For exploring the effect of gap junctional intercellular communication (GJIC) on the bystander effect mediated by HSV-TK/GCV system and investigating the chemical modulation of GJIC and bystander effect， the GJIC of five cell lines named ACHN， HeLa， NIH-3T3， Cos-7 and L-02 were detected by the Scrape-loading dye transfer assay(SLDT)， and their susceptiveness to HSV-TK/GCV approach and the bystander tumoricidal effect were determined. In addition， the influence of apigenin and 18-α-glycyrrhetinic acid(AGA)， which were reported as GJIC up- and down-regulator， on the GJIC of certain cell lines and on the bystander effect induced by HSV-TK/GCV were observed. It was manifested that the susceptiveness to HSV-TK/GCV approach and the magnitude of bystander effect were higher in NIH-3T3， Cos-7， and L-02 cells which manifested excellent GJIC than in ACHN and HeLa cells which showed poor GJIC(P<0.001). It also demonstrated that apigenin could significantly improve the GJIC of ACHN cells while could not exercise any influence on that of HeLa cells， on the other hand， AGA could effectively inhibit the GJIC of the three target cell lines. Accordingly， apigenin markedly enhanced the bystander effect of ACHN but had little effect on the bystander effect of HeLa， and AGA inhibited the bystander effect of the above three cell lines. In conclusion， the cellular inherent GJIC positively correlates to the sensitivities of GCV in the cells modified with HSV-TK gene and to the bystander effect mediated by this approach， and the magnitude of bystander effect were altered corresponding to the chemical modulation of target cells.

CSTR: 32200.14.cjcb.2004.02.0015