title: Nimotuzumab suppresses epithelial-mesenchymal transition and enhances apoptosis in low-dose UV-C treated salivary adenoid cystic carcinoma cell lines in vitro.
abstract: Salivary adenoid cystic carcinoma (SACC), which is one of the most common malignant tumors of the salivary glands, is associated with a poor long-term outcome. There are currently few therapeutic options for patients with SACC. Recent studies have shown the potential of the application of ultraviolet-C (UV-C) irradiation for the treatment of human cancer. In the present study, we investigated the effects of UV-C in the SACC cell lines SACC-83 and SACC-LM. High-dose UV-C (200 J/m) induced apoptosis and inhibited colony formation significantly. However, low-dose UV-C (10 J/m), which had little effect on apoptosis and colony formation, increased the ability of migration in SACC cells accompanied by a decrease in E-cadherin and an increase in vimentin, suggesting the occurrence of epithelial-mesenchymal transition (EMT). Low-dose UV-C (10 J/m) also resulted in upregulation of the phosphorylated forms of epidermal growth factor receptor (EGFR) and Akt (p-EGFR and p-Akt, respectively). Pretreatment with Nimotuzumab, an anti-EGFR monoclonal antibody, reversed the EMT as well as upregulation of p-EGFR/p-Akt induced by UV-C. Moreover, Nimotuzumab enhanced UV-C induced apoptosis and inhibition of colony formation. Our results indicate that EMT exerts a protective effect against apoptosis induced by low-dose UV-C. Thus, the combined application of Nimotuzumab and low-dose UV-C in vitro has an advantageous antitumor effect in SACC compared with the application of UV-C alone.
authors.affiliation: aDepartment of Oral and Maxillofacial Surgery bCentral Laboratory, Peking University School and Hospital of Stomatology, Beijing, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xi-Yuan
authors.initials: XY
authors.lastname: Ge
authors.forename: Shu-Ming
authors.initials: SM
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Huang
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.forename: Jia
authors.initials: J
authors.lastname: Fu
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Zhang
authors.forename: Sheng-Lin
authors.initials: SL
authors.lastname: Li
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015820:Cadherins / Q000378:metabolism; D003528:Carcinoma, Adenoid Cystic / Q000473:pathology*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000528:radiation effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000528:radiation effects; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation; D012468:Salivary Gland Neoplasms / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D014466:Ultraviolet Rays; D014746:Vimentin / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D015820:Cadherins; D014746:Vimentin; C501466:nimotuzumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D051058:Oncogene Protein v-akt