机构：[a]Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, People’s Republic of China[b]Department of Anesthesia, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510260, People’s Republic of China[c]Department of Anesthesia, The Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, People’s Republic of China中山大学附属第二医院[d]Department of Hepatobiliary Surgery, Guangdong Province Traditional Chinese Medical Hospital, Guangzhou 510120, People’s Republic of China大德路总院外科大德路总院外一科广东省中医院[e]Department of Pharmacy, The First Affiliated Hospital, Bengbu Medical College, Bengbu 233004, People’s Republic of China[f]Department of Gynaecology and Obstetrics, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, People’s Republic of Chinaa中山大学附属第三医院
Some of lipophilic statins have been reported to enhance toxicities induced by antineoplastic agents but the underling mechanism is unclear. The authors investigated the involvement of Cx43-mediated gap junction intercellular communication (GJIC) in the effect of simvastatin on the cellular toxicity induced by etoposide in this study. The results showed that a major component of the cytotoxicity of therapeutic levels of etoposide is mediated by gap junctions composed of connexin 43(Cx43) and simvastatin at the dosage which does not induce cytotoxicity enhances etoposide toxicity by increasing gap junction coupling. The augmentative effect of simvastatin on GJIC was related to the inhibition of PKC-mediated Cx43 phosphorylation at ser368 and subsequent enhancement of Cx43 membrane location induced by the agent. The present study suggests the possibility that upregulation of gap junctions may be utilized to increase the efficacy of anticancer chemotherapies. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
基金：
This work was supported by the grant for the construction of thetechnique plate for evaluation of the pharmacodynamics of newdrugs in Xinjiang from the Department of Science and Technologyof Xinjiang province (no. 201233150), the Fundamental ResearchFunds for the Central Universities (no. 10YKPY32), and GuangdongProvince Science and Technology Project (2010B031600199).
第一作者机构：[a]Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, People’s Republic of China[b]Department of Anesthesia, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510260, People’s Republic of China
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推荐引用方式(GB/T 7714)：
Lingzhi Wang,Yanni Fu,Jianxin Peng,et al.Simvastatin-induced up-regulation of gap junctions composed of connexin 43 sensitize Leydig tumor cells to etoposide: An involvement of PKC pathway[J].TOXICOLOGY.2013,312:149-157.doi:10.1016/j.tox.2013.08.013.
APA：
Lingzhi Wang,Yanni Fu,Jianxin Peng,Dengpan Wu,Meiling Yu...&Liang Tao.(2013).Simvastatin-induced up-regulation of gap junctions composed of connexin 43 sensitize Leydig tumor cells to etoposide: An involvement of PKC pathway.TOXICOLOGY,312,
MLA：
Lingzhi Wang,et al."Simvastatin-induced up-regulation of gap junctions composed of connexin 43 sensitize Leydig tumor cells to etoposide: An involvement of PKC pathway".TOXICOLOGY 312.(2013):149-157
