AIM By investigating the
bystander effect enchanced by all trans retionic acid (ATRA) in herpes simplex virus thymidine
kinase gene/ganciclovir(HSV tK/GCV) system and with relation to Cx43 mRNA
expression to provide experimental basis for heightening therapy efficiency of TK suicide gene and exploring mechanism of enchancement role. METHODS Enhancement of the
bystander effect in HSV tK/GCV and Cx43 mRNA expression in cervical carcinoma ME180 and ME180/TK transfection cells were examined by using Polybrene transfection, fluor quantitative RT PCR techanques. RESULTS ME180 and ME180/TK mixed cells were suppressed by gradational increase in ATRA concentration in HSV tk/GCV system. The survival rate of ME180+ME180/TK mixed cells decreased with the increase in ME180/TK ratio. In the presence of 2 mg·L -1 GCV, the more lower survival rate was observed at any given mixture of ME180 and ME180/TK cells exposed to 10 -8 mol·L -1 ATRA compared with that in the absence of ATRA (0 mol·L -1 ) (P<0.05). However, enchancement of bystander mediated cell killing occurred only in the concentration range of 10 -8 -10 -10 mol·L -1 of ATRA. The results of RT PCR showed that comparing with non ATRA treated ME180 cells, the ratio of relative copy number of Cx43 mRNA increased by 2.65 and 1.84 fold in ME180 cells exposed to 10 -8 and 10 -10 mol·L -1 ATRA, respectively. CONCLUSION In cervical carcinoma ME180 cell line, ATRA enhances the bystander effect in the HSV tK/GCV system. Its main mechanism of enchancement is up regulation of Cx43 mRNA expression in transcription level.