Neuronal uptake transporters contribute to oxaliplatin neurotoxicity in mice

被引：44

作者：

Huang, Kevin M. ^{[1
,2
]}

Leblanc, Alix F. ^{[1
,2
]}

Uddin, Muhammad Erfan ^{[1
,2
]}

Kim, Ji Young ^{[1
,2
]}

Chen, Mingqing ^{[1
,2
]}

Eisenmann, Eric D. ^{[1
,2
]}

Gibson, Alice A. ^{[1
,2
]}

Li, Yang ^{[1
,2
]}

Hong, Kristen W. ^{[1
,2
]}

DiGiacomo, Duncan ^{[1
,2
]}

Xia, Sherry H. ^{[1
,2
]}

Alberti, Paola ^{[3
,4
]}

Chiorazzi, Alessia ^{[3
,4
]}

Housley, Stephen N. ^{[5
,6
]}

Cope, Timothy C. ^{[5
,6
]}

Sprowl, Jason A. ^{[7
]}

Wang, Jing ^{[2
,8
]}

Loprinzi, Charles L. ^{[9
]}

Noonan, Anne ^{[2
,10
]}

Lustberg, Maryam B. ^{[2
,10
]}

Cavaletti, Guido ^{[3
,4
]}

Pabla, Navjot ^{[1
,2
]}

Hu, Shuiying ^{[1
,2
]}

Sparreboom, Alex ^{[1
,2
]}

机构：

[1] Ohio State Univ, Coll Pharm, Div Pharmaceut & Pharmacol, Columbus, OH 43210 USA

[2] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA

[3] Univ Milano Bicocca, Sch Med & Surg, Monza, Italy

[4] Milan Ctr Neurosci, NeuroMI, Milan, Italy

[5] Georgia Inst Technol, Sch Biol Sci, Atlanta, GA 30332 USA

[6] Georgia Inst Technol, Coulter Dept Biomed Engn, Atlanta, GA 30332 USA

[7] SUNY Buffalo, Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Buffalo, NY USA

[8] Ohio State Univ, Coll Med, Dept Canc Biol & Genet, Columbus, OH 43210 USA

[9] Mayo Clin, Dept Oncol, Ctr Comprehens Canc, Rochester, MN USA

[10] Ohio State Univ, Coll Med, Dept Internal Med, Div Med Oncol, Columbus, OH 43210 USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2020年 / 130卷 / 09期

关键词：

CISPLATIN; NEUROPATHY; DISPOSITION; TOXICITY; CELLS; OCT2;

D O I：

10.1172/JCI136796

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Peripheral neurotoxicity is a debilitating condition that afflicts up to 90% of patients with colorectal cancer receiving oxaliplatin-containing therapy. Although emerging evidence has highlighted the importance of various solute carriers to the toxicity of anticancer drugs, the contribution of these proteins to oxaliplatin-induced peripheral neurotoxicity remains controversial. Among candidate transporters investigated in genetically engineered mouse models, we provide evidence for a critical role of the organic cation transporter 2 (OCT2) in satellite glial cells in oxaliplatin-induced neurotoxicity, and demonstrate that targeting OCT2 using genetic and pharmacological approaches ameliorates acute and chronic forms of neurotoxicity. The relevance of this transport system was verified in transporter-deficient rats as a secondary model organism, and translational significance of preventive strategies was demonstrated in preclinical models of colorectal cancer. These studies suggest that pharmacological targeting of OCT2 could be exploited to afford neuroprotection in cancer patients requiring treatment with oxaliplatin.

引用

页码：4601 / 4606

页数：6

共 29 条

[1] A review on oxaliplatin-induced peripheral nerve damage [J].