title: MEK inhibitor diminishes nasopharyngeal carcinoma (NPC) cell growth and NPC-induced osteoclastogenesis via modulating CCL2 and CXCL16 expressions.
abstract: Nasopharyngeal carcinoma (NPC) is a common malignancy in southern China and Southeast Asia. NPC frequently metastasizes to the bone in advanced patients resulting in high mortality. The molecular mechanisms for NPC development and cancer-induced bone lesions are unclear. In this study, we firstly determined chemokine receptor CCR2 and CXCR6 expressions in clinical specimens and CNE2, SUNE1, CNE1, and HK1 cell lines. Then, we measured chemokine CCL2 and CXCL16 production in these NPC cell lines by ELISA. Expression levels of these chemokines and their receptors were observed to positively correlate with tumor aggressiveness. Furthermore, U0126 (MEK inhibitor) was used to treat these NPC cell lines. CCL2 and CXCL16 expression levels and cell proliferation were significantly inhibited by U0126 in a dose- and time-dependent manner. Finally, we collected conditioned medium (CM) from NPC cell cultures in the presence of U0126 treatment. When mouse bone marrow non-adherent cells were treated with the CM, the numbers of multinucleated osteoclast formation were dramatically diminished. These results indicate that MEK inhibitor diminishes NPC cell proliferation and NPC-induced osteoclastogenesis via modulating CCL2 and CXCL16 expressions. This study provides novel therapeutic targets such as CCL2/CCR2 and CXCL16/CXCR6 for advanced NPC patients.
authors.affiliation: Key Laboratory of Longevity and Aging-related Diseases, Ministry of Education, Nanning, Guangxi, China.|Center for Translational Medicine, Guangxi Medical University, No.22 Shuangyong Road, 1416 Pharmacology & Biomedical Sciences Building, Nanning, Guangxi, 530021, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Longevity and Aging-related Diseases, Ministry of Education, Nanning, Guangxi, China.|Center for Translational Medicine, Guangxi Medical University, No.22 Shuangyong Road, 1416 Pharmacology & Biomedical Sciences Building, Nanning, Guangxi, 530021, China.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Zou
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, China.
authors.forename: Chao-Nan
authors.initials: CN
authors.lastname: Qian
authors.affiliation: Key Laboratory of Longevity and Aging-related Diseases, Ministry of Education, Nanning, Guangxi, China.|Center for Translational Medicine, Guangxi Medical University, No.22 Shuangyong Road, 1416 Pharmacology & Biomedical Sciences Building, Nanning, Guangxi, 530021, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Longevity and Aging-related Diseases, Ministry of Education, Nanning, Guangxi, China.|Center for Translational Medicine, Guangxi Medical University, No.22 Shuangyong Road, 1416 Pharmacology & Biomedical Sciences Building, Nanning, Guangxi, 530021, China.
authors.forename: Junlin
authors.initials: J
authors.lastname: Shi
authors.affiliation: Key Laboratory of Longevity and Aging-related Diseases, Ministry of Education, Nanning, Guangxi, China.|Center for Translational Medicine, Guangxi Medical University, No.22 Shuangyong Road, 1416 Pharmacology & Biomedical Sciences Building, Nanning, Guangxi, 530021, China.
authors.forename: Yudui
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Key Laboratory of Longevity and Aging-related Diseases, Ministry of Education, Nanning, Guangxi, China. jzhangqi@gmail.com.|Center for Translational Medicine, Guangxi Medical University, No.22 Shuangyong Road, 1416 Pharmacology & Biomedical Sciences Building, Nanning, Guangxi, 530021, China. jzhangqi@gmail.com.|Department of Pathology and Internal Medicine, University of Michigan, Ann Arbor, MI, USA. jzhangqi@gmail.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Longevity and Aging-related Diseases, Ministry of Education, Nanning, Guangxi, China. luyi5555@hotmail.com.|Center for Translational Medicine, Guangxi Medical University, No.22 Shuangyong Road, 1416 Pharmacology & Biomedical Sciences Building, Nanning, Guangxi, 530021, China. luyi5555@hotmail.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D002070:Butadienes / Q000008:administration & dosage; D002277:Carcinoma; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*; D051379:Mice; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009570:Nitriles / Q000008:administration & dosage; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D051116:Receptors, Scavenger / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D002070:Butadienes; C111835:CCL2 protein, human; C423727:CXCL16 protein, human; D018932:Chemokine CCL2; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D017077:Culture Media, Conditioned; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D051116:Receptors, Scavenger; C113580:U 0126; D020930:MAP Kinase Kinase Kinases
keywords: CCL2/CCR2; CXCL16/CXCR6; Nasopharyngeal carcinoma; Osteoclastogenesis; U0126