Gap junctions propagate opposite effects in normal and tumor testicular cells in response to cisplatin
Gap junctions propagate opposite effects in normal and tumor testicular cells in response to cisplatin
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缝隙连接在正常和肿瘤睾丸细胞中传播对顺铂的相反作用
DOI：
10.1016/j.canlet.2011.11.019
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发表时间：
2012-04-28
期刊：
影响因子：
9.7
通讯作者：
Harris, Andrew L.
中科院分区：
文献类型：
--
作者：
Hong, Xiaoting;Wang, Qin;Harris, Andrew L.
缝隙连接在化疗期间在肿瘤细胞之间传播毒性作用，但也可以通过相同的机制增强对正常细胞的杀伤。我们发现，间隙连接细胞间通讯（GJIC）对顺铂毒性的影响在正常和肿瘤睾丸细胞之间是不同的。通过几种不同的操作（无细胞接触、药理学抑制、siRNA抑制）中的每一种下调GJIC降低了肿瘤细胞中的顺铂细胞毒性，但增强了正常细胞中的顺铂细胞毒性。正常细胞中GJIC下调导致的毒性增强与DNA链间交联增加相关。因此，GJIC保护正常细胞免受顺铂毒性，同时增强其在肿瘤细胞中的毒性，表明GJIC的增强/维持增加治疗功效，同时降低脱靶毒性。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Gap junctions propagate toxic effects among tumor cells during chemotherapy, but could also enhance killing of normal cells by the same mechanism. We show that the effect of gap junctional intercellular communication (GJIC) on cisplatin toxicity differs between normal and tumor testicular cells. Downregulation of GJIC by each of several different manipulations (no cell contact, pharmacological inhibition, siRNA suppression) decreased cisplatin cytoxicity in tumor cells but enhanced it in normal cells. Enhanced toxicity due to GJIC downregulation in normal cells correlated with increased DNA interstrand crosslinks. Thus, GJIC protects normal cells from cisplatin toxicity while enhancing it in tumor cells, suggesting that enhancement/maintenance of GJIC increases therapeutic efficacy while decreasing off-target toxicity. (C) 2011 Elsevier Ireland Ltd. All rights reserved.