title: Combination of NTP with cetuximab inhibited invasion/migration of cetuximab-resistant OSCC cells: Involvement of NF-κB signaling.
abstract: Although the epidermal growth factor receptor (EGFR) is an established target in head-and-neck cancer (HNC), resistance to EGFR-targeted therapy mediated by various mechanisms has been reported. Therefore, a combination strategy to overcome resistance to EGFR mono-targeted therapy is clinically required. We have previously demonstrated that non-thermal atmospheric pressure plasma (NTP) induces death of various cancer cells, including oral squamous cancer (OSCC) cells. In this study, we report for the first time that combining NTP treatment with cetuximab led to inhibition of migration and invasion in cetuximab-resistant OSCC cells, which could be a promising strategy to overcome resistance to anti-EGFR therapy. NTP induced deactivation of NF-κB in SCCQLL1 cells, but not in MSKQLL1 cells. In addition, NTP increased the expression level of E-cadherin, and decreased those of vimentin, Slug, Snail, matrix metalloproteinase (MMP)-2, -9, and activities of MMPs. Moreover, NF-κB upregulation using cDNA diminished the combination effect of NTP on invasion, migration and related signals. Taken together, these results indicate that the combination of NTP with cetuximab can decrease invasiveness in cetuximab-resistant OSCCs through a novel mechanism involving the NF-κB pathway. These findings show the therapeutic potential of treatment that combines NTP and cetuximab in OSCC.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Chang
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Republic of Korea.
authors.forename: Sung Un
authors.initials: SU
authors.lastname: Kang
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Republic of Korea.
authors.forename: Yoo Seob
authors.initials: YS
authors.lastname: Shin
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Republic of Korea.
authors.forename: Seong Jin
authors.initials: SJ
authors.lastname: Seo
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Republic of Korea.
authors.forename: Yeon Soo
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Electrical and Computer Engineering, Ajou University, Suwon, Republic of Korea.
authors.forename: Sang Sik
authors.initials: SS
authors.lastname: Yang
authors.affiliation: Department of Molecular Science and Technology and Department of Life Science, Ajou University, Suwon, Republic of Korea.
authors.forename: Jong-Soo
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Molecular Science and Technology and Department of Life Science, Ajou University, Suwon, Republic of Korea.
authors.forename: Eunpyo
authors.initials: E
authors.lastname: Moon
authors.affiliation: PSM America Inc., Colorado Springs, CO, USA.
authors.forename: Keunho
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Republic of Korea.
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000068818:Cetuximab / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004357:Drug Synergism; D058750:Epithelial-Mesenchymal Transition; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D058626:Plasma Gases / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D058626:Plasma Gases; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000068818:Cetuximab