Upregulation of the mevalonate pathway by cholesterol depletion abolishes tolerance to N-bisphosphonate induced Vγ9Vδ2 T cell cytotoxicity in PC-3 prostate cancer cells

被引：9

作者：

Arkko, S. ^{[1
]}

Zlatev, H. P. ^{[1
]}

Monkkonen, H. ^{[1
]}

Raikkonen, J. ^{[1
]}

Benzaid, I.

Clezardin, R. ^{[2
]}

Monkkonen, J. ^{[1
]}

Maatta, J. A. ^{[1
,3
]}

机构：

[1] Univ Eastern Finland, Sch Pharm, Fac Hlth Sci, Kuopio, Finland

[2] Univ Lyon, INSERM, UMR 1033, UFR Med Lyon Est, Lyon, France

[3] Univ Turku, Inst Biomed, Dept Cell Biol & Anat, Turku, Finland

来源：

CANCER LETTERS | 2015年 / 357卷 / 01期

基金：

芬兰科学院;

关键词：

N-bisphosphonate; Zoledronic acid; Phosphoantigen; Cancer resistance; Gamma-delta T cell; NITROGEN-CONTAINING BISPHOSPHONATES; FARNESYL PYROPHOSPHATE SYNTHASE; ATP ANALOG FORMATION; ZOLEDRONIC ACID; IN-VIVO; MULTIDRUG-RESISTANCE; INHIBITION; APOPTOSIS; BINDING; GROWTH;

D O I：

10.1016/j.canlet.2014.11.030

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Zoledronate (ZOL) inhibits farnesyl pyrophosphate synthase leading to intracellular accumulation of isopentenyl pyrophosphate/triphosphoric acid 1-adenosin-5'yl ester 3-(3-methylbut-3-enyl) ester (IPP/ApppI). Cytotoxic V gamma 9V delta 2 T cells have been shown to recognize IPP/ApppI in breast cancer cells. Further, human breast cancer cells have been shown to differ remarkably in their ZOL treatment induced IPP/ApppI production and responses to that. In this communication we analysed the responsiveness of prostate cancer cells PC-3 and,DU-145, Caki-2 renal carcinoma cells and U87MG glioblastoma cells to ZOL treatment, and the subsequent activation of V gamma 9V delta 2 T-cell cytotoxicity. Of the cell lines tested, PC-3 cells were not susceptible to V gamma 9V delta 2 T-cell cytotoxicity due to low activity of the mevalonate pathway and low amount of IPP formed. However, the resistance of PC-3 cells to V gamma 9V delta 2 T-cell cytotoxicity could be abrogated by upregulation of the mevalonate pathway through cholesterol depletion. (c) 2014 Elsevier Ireland Ltd. All rights reserved.

引用

页码：279 / 285

页数：7

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