title: Niflumic acid exhibits anti-tumor activity in nasopharyngeal carcinoma cells through affecting the expression of ERK1/2 and the activity of MMP2 and MMP9.
abstract: Niflumic acid (NFA) was known to inhibit cell proliferation or migration in several types of cancer. However, the function of NFA in human nasopharyngeal carcinoma (NPC) cells was not clarified. The proliferation of NPC cell line CNE-2Z cells with NFA treatment was detected using the cell counting kit-8 method and transwell assay was employed to assess the effect of NFA on the CNE-2Z cell migration and invasion. The activity of MMP2 and MMP9 was detected by Gelatin Zymography. Cell cycle distribution and apoptosis were detected using flow cytometry. In vitro pull-down assay, western blot, and computational technique were applied to investigate the NFA regulating signaling pathway. Our results indicated that the growth capacity and colony formation potential of CNE-2Z cells in soft agar were significantly suppressed by treatment with NFA. NFA inhibited the proliferation of CNE-2Z cells in a concentration and time-dependent manner. NFA exerted an S phase arrest on the CNE-2Z cells in a concentration-dependent manner, while promoting apoptosis in a dose-dependent manner. Migration and invasion potential of CNE-2Z cells were decreased by NFA treatment in vitro. In vitro pull-down assay and molecular modeling indicated that NFA directly bound with early respond kinase 1 (ERK1). Finally, the anti-tumor effect of NFA was suggested to be mediated by inhibiting early respond kinases (ERK) expression and the MMP2 and MMP9 activities. NFA has proliferation-inhibiting, invasion-suppressing, cell cycle-blocking and apoptosis-promoting effects on CNE-2Z cells through regulation of ERK/MAPK and our results indicates that NFA may serve as a candidate of anticancer drug for NPC.
authors.affiliation: Sino-American Cancer Research Institute, Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical University Dongguan 523808, P. R. China.
authors.forename: Shengqun
authors.initials: S
authors.lastname: Luo
authors.affiliation: Sino-American Cancer Research Institute, Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical University Dongguan 523808, P. R. China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Huang
authors.affiliation: Sino-American Cancer Research Institute, Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical University Dongguan 523808, P. R. China.
authors.forename: Ziyou
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Sino-American Cancer Research Institute, Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical University Dongguan 523808, P. R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wan
authors.affiliation: Sino-American Cancer Research Institute, Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical University Dongguan 523808, P. R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.affiliation: Sino-American Cancer Research Institute, Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical University Dongguan 523808, P. R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liao
authors.affiliation: Sino-American Cancer Research Institute, Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical University Dongguan 523808, P. R. China.
authors.forename: Chuyan
authors.initials: C
authors.lastname: Chen
authors.affiliation: Sino-American Cancer Research Institute, Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical University Dongguan 523808, P. R. China.
authors.forename: Huahui
authors.initials: H
authors.lastname: Li
authors.affiliation: Sino-American Cancer Research Institute, Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical University Dongguan 523808, P. R. China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Li
authors.affiliation: Sino-American Cancer Research Institute, Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical University Dongguan 523808, P. R. China.
authors.forename: Liyong
authors.initials: L
authors.lastname: Chen
authors.affiliation: Sino-American Cancer Research Institute, Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical University Dongguan 523808, P. R. China.
authors.forename: Zunnan
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Sino-American Cancer Research Institute, Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical University Dongguan 523808, P. R. China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: He
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009544:Niflumic Acid / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D009544:Niflumic Acid; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: MAPK/ERK; MMP2; MMP9; Niflumic acid (NFA); molecular modeling; nasopharyngeal carcinoma