Celecoxib reverts oxaliplatin-induced neuropathic pain through inhibiting PI3K/Akt2 pathway in the mouse dorsal root ganglion.
Exp Neurol
; 275 Pt 1: 11-6, 2016 Jan.
Article
em En
| MEDLINE
| ID: mdl-26546510
ABSTRACT
Oxaliplatin (OXA) is the common and extremely potent anti-advanced colorectal cancer chemotherapeutic. Accumulating evidence reveals that OXA evokes mechanical and cold hypersensitivity. However, the mechanism underlying these bothersome and dose-limiting adverse effects is poorly understood. It is well known that cyclooxygenase-2 (COX-2) as well as phosphoinositide 3-kinase (PI3K)/Akt signaling mediate the neuropathic pain. But it is still unclear whether COX-2 or PI3K/Akt signaling participates in the regulation of OXA-induced hypersensitivity, as well as the linkage between COX-2 and PI3K/Akt signaling in mediating OXA-induced hypersensitivity. In this paper, we investigated the anti-nociceptive effect of celecoxib, an inhibitor of COX-2, on the OXA-induced neuropathic pain. We found that OXA increased the expression of cyclooxygenase-2 (COX-2) and Akt2 in the lumbar 4-5 (L4-5) dorsal root ganglion (DRG). And the administration of celecoxib alleviates the OXA-induced hypersensitivity and suppresses the COX-2 and PI3K/Akt2 signaling. Our findings showed that COX-2 and PI3K/Akt2 signaling in DRG contributed to the OXA-induced neuropathic pain. In addition, celecoxib enhanced the OXA-induced mortality of the human colon cancer cell line HCT-116. Thus, celecoxib might play a dual role in colorectal cancer treatment alleviating OXA-induced neuropathic pain and facilitating the anti-tumor effects of OXA through their synergistic role.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Proteínas Proto-Oncogênicas c-akt
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Inibidores de Ciclo-Oxigenase 2
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Celecoxib
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Gânglios Espinais
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Inibidores de Fosfoinositídeo-3 Quinase
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Neuralgia
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article