[Enhancement of the bystander effect by tanshinone IIA in HSV-tK/GCV system is related to expression of connexin 43 mRNA].
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.


CONCLUSIONS
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.
Huang
Guang-Qi
GQ
Institute of Cancer Research, West China Hospital, Sichuan University, Chengdu 610041, China. Lixinling@chengda.com
Song
Yi
Y
Zhang
Jie
J
Lu
Yan-Rong
YR
Xiao
Lin
L
Yang
Yuan
Y
Guo
Yuan-Biao
YB
D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D024201:Bystander Effect; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018031:Connexin 43 / Q000235:genetics*; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology*; D015316:Genetic Therapy; D006801:Humans; D010616:Phenanthrenes / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018139:Simplexvirus / Q000201:enzymology*; D013937:Thymidine Kinase / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000628:therapy*
D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D018031:Connexin 43; D010616:Phenanthrenes; C021751:tanshinone; D013937:Thymidine Kinase; D015774:Ganciclovir