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: Jae Won Chang, Sung Un Kang, Yoo Seob Shin, Seong Jin Seo, Yeon Soo Kim, Sang Sik Yang, Jong-Soo Lee, Eunpyo Moon, Keunho Lee, Chul-Ho Kim
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 18208 (Dec 14 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 26655729 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• Plasma Gases
• Tumor Suppressor Protein p53
• ErbB Receptors
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9
• Cetuximab

Topics

• Apoptosis (drug effects)
• Carcinoma, Squamous Cell (genetics, metabolism)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cetuximab (pharmacology)
• Drug Resistance, Neoplasm (genetics)
• Drug Synergism
• Epithelial-Mesenchymal Transition
• ErbB Receptors (genetics, metabolism)
• Humans
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Mouth Neoplasms (genetics, metabolism)
• NF-kappa B (metabolism)
• Plasma Gases (pharmacology)
• Signal Transduction (drug effects)
• Tumor Suppressor Protein p53 (metabolism)