title: The cancer pain related factors affected by celecoxib together with cetuximab in head and neck squamous cell carcinoma.
abstract: Pain is the most disruptive influence on the quality of prognosis among head and neck squamous cell carcinoma (HNSCC) patients. The development of pain is closely associated with tumor growth and inflammation in the cancer patients. Notably, cyclooxygenase-2 (COX-2) is an important mediator during inflammation. Celecoxib, a selective inhibitor of COX-2, was hailed as a promising chemopreventive agent for HNSCC. Dose-dependent cardiac toxicity limits long-term use of celecoxib. However, the toxicity can be diminished by lowering the dosage. In this study, we hypothesized that a combinatory strategy to reduce cancer pain via two distinct pathways, tumor grown inhibition and inflammation blockade, which would enhance analgesia effect induced by HNSCC. We found that treatment of cetuximab (C225), a monoclonal anti-epidermal growth factor receptor (EGFR) antibody, with low-dose celecoxib results in a more pronounced anticancer effect in HNSCC than either agent alone. More noticeably, the combination could downregulate the phosphorylation of constitutively active extracellular signal regulated kinase (ERK) in CAL-27 and Fadu cells. Furthermore, combination therapy enhancing S phase arrest and downregulating cyclin D1 was observed in Fadu cells. The COX-2 expression was significantly blocked by celecoxib combined with C225, and other cancer pain related factors, such as ET-1 and NGF, was also downregulated by combination treatment. Taken together, these results strongly suggest that combination of celecoxib with C225 holds potential as a new therapy strategy in developing cancer pain treatment in HNSCC.
authors.affiliation: Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Road 639, Shanghai 200011, China.
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Road 639, Shanghai 200011, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Road 639, Shanghai 200011, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Road 639, Shanghai 200011, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Road 639, Shanghai 200011, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Road 639, Shanghai 200011, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.affiliation: Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Road 639, Shanghai 200011, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Road 639, Shanghai 200011, China. Electronic address: dzfc2013@163.com.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Road 639, Shanghai 200011, China. Electronic address: dr_jianghong@163.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000068579:Celecoxib / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000068818:Cetuximab / Q000008:administration & dosage*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D010146:Pain / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D000068579:Celecoxib; D000068818:Cetuximab
keywords: COX-2; Celecoxib; Cetuximab; ET-1; HNSCC; NGF