title: Celecoxib reverts oxaliplatin-induced neuropathic pain through inhibiting PI3K/Akt2 pathway in the mouse dorsal root ganglion.
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.
authors.affiliation: Department of Histology and Embryology, Medical College, Nanchang University, Bayi Road 461, Nanchang 330006, China.
authors.forename: Shu-Ping
authors.initials: SP
authors.lastname: Jiang
authors.affiliation: Department of Pathology, First Affiliated Hospital of Nanchang University, Yongwaizheng Street 17, Nanchang 330006, China.
authors.forename: Zhen-Dong
authors.initials: ZD
authors.lastname: Zhang
authors.affiliation: Department of Animal Science, Medical College, Nanchang University, Bayi Road 461, Nanchang 330006, China.
authors.forename: Lu-Mei
authors.initials: LM
authors.lastname: Kang
authors.affiliation: Department of Histology and Embryology, Medical College, Nanchang University, Bayi Road 461, Nanchang 330006, China.
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Wang
authors.affiliation: Department of Histology and Embryology, Medical College, Nanchang University, Bayi Road 461, Nanchang 330006, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Histology and Embryology, Medical College, Nanchang University, Bayi Road 461, Nanchang 330006, China. Electronic address: jxchp2000@126.com.
authors.forename: Hong-Ping
authors.initials: HP
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000068579:Celecoxib / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D051379:Mice; D009437:Neuralgia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D009944:Organoplatinum Compounds; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000077150:Oxaliplatin; D051057:Proto-Oncogene Proteins c-akt; D000068579:Celecoxib
keywords: Akt2; Celecoxib; Colon cancer cell; Cyclooxygenase-2; Neuropathic pain; Oxaliplatin