Gap junctions propagate opposite effects in normal and tumor testicular cells in response to cisplatin

被引：51

作者：

Hong, Xiaoting ^{[1
]}

Wang, Qin ^{[1
]}

Yang, Yan ^{[1
]}

Zheng, Suping ^{[1
]}

Tong, Xuhui ^{[2
]}

Zhang, Suzhi ^{[1
]}

Tao, Liang ^{[1
]}

Harris, Andrew L. ^{[3
]}

机构：

[1] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Pharmacol, Guangzhou 510080, Guangdong, Peoples R China

[2] Bengbu Med Coll, Dept Pharm, Bengbu 233000, Peoples R China

[3] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Physiol & Pharmacol, Newark, NJ 07103 USA

来源：

CANCER LETTERS | 2012年 / 317卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Cancer; Cisplatin; Chemotherapy; Gap junction; Bystander effect; INTERCELLULAR COMMUNICATION; CANCER-CELLS; CONNEXIN EXPRESSION; ANTICANCER DRUGS; UP-REGULATION; CHANNELS; GLUTATHIONE; GROWTH; GENE; HEMICHANNELS;

D O I：

10.1016/j.canlet.2011.11.019

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：165 / 171

页数：7

共 57 条

[1]

HDACi phenylbutyrate increases bystander killing of HSV-tk transfected glioma cells [J].