Objective: To investigate enhancement of the bystander effect by tanshinone IIA (Tan) in HSV-tK/GCV system and the correlation with expression of connexin 43 mRNA.
Methods: The cytotoxic effect in HSV-tK/GCV in cervical carcinoma cell line ME180 (ME) and ME/TK was examined by MTT assays. Cx43 mRNA expression was detected by fluor-quantitative RT-PCR.
Results: Tan markedly increased sensitivity of ME/TK cells for GCV in HSV-tK/GCV system. In the presence of 2 micro g/ml GCV, compared with the absence of Tan (0 mol/L), an obvious decrease in survival rate was seen at any given mixture of ME and ME/TK cells exposed to 1.3 x 10(-9) mol/L Tan. Statistics showed significant difference (P < 0.05). However, enhancement of bystander mediated cell killing occurred only in the range of Tan concentrations used (1.3 x 10(-8), 1.3 x 10(-9) mol/L). RT-PCR showed that the ratio of relative copy number of Cx43 mRNA increased by 8.83 and 8.47-fold in ME cells exposed to 1.3 x 10(-8) and 1.3 x 10(-9) mol/L Tan, respectively.
Conclusion: For the first time we report that in cervical carcinoma ME180 cell line, Tan possesses a remarkable enhancing role on the bystander effect in the HSV-tK/GCV system. It is associated with up-regulation of Cx43 mRNA expression.