title: NS-398 promotes pancreatic cancer cell invasion by CD147 and MMP-2 via the activation of P38.
abstract: The overexpression or abnormal activation of cyclo‑oxygenase‑2 (COX‑2) has been reported in pancreatic cancer cells. NS‑398, a selective inhibitor of COX‑2, is unable to inhibit pancreatic cancer cell proliferation, as determined by a Cell Counting Kit 8 assay. However, it does increase cancer cell invasiveness, and therefore the invasiveness of the PANC‑1 cells was determined, along with the activation of P38, which was assessed by western blotting. In the present study, to evaluate the mechanisms underlying the action of NS‑398 in pancreatic cancer cells, PANC‑1 cells were treated with NS‑398, and the invasion signaling pathways of cluster of differentiation (CD)147‑matrix metalloproteinase (MMP)‑2 and mitogen‑activated protein kinases were evaluated. The results showed that NS‑398‑induced the expression of CD147 and MMP‑2 via the activation of P38, which was involved in antiproliferative activity and induced pancreatic cancer cell invasiveness. The PANC‑1 cells were also co‑treated with CD147 small interfering (si)RNA and NS‑398, and it was found that the NS‑398‑induced activation of P38 was not inhibited by CD147 siRNA, however, the expression of MMP‑2 was inhibited. CD147 siRNA inhibited the invasiveness of the pancreatic cancer cells induced by NS‑398, but also restored NS‑398‑induced antiproliferative activity. These data indicated that P38 in the pancreatic cancer cells was non‑specifically activated by NS‑398. This activation induced the expression of CD147‑MMP‑2, opposed the antiproliferative activity of NS‑398 and increased the invasiveness of the PANC‑1 cells.
authors.affiliation: Department of Gastroenterology, The Tenth Hospital Affiliated to Tongji University, Shanghai 200072, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, The Tenth Hospital Affiliated to Tongji University, Shanghai 200072, P.R. China.
authors.forename: Xuan-Fu
authors.initials: XF
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, The Tenth Hospital Affiliated to Tongji University, Shanghai 200072, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, The Tenth Hospital Affiliated to Tongji University, Shanghai 200072, P.R. China.
authors.forename: Mao-Chun
authors.initials: MC
authors.lastname: Tang
authors.affiliation: Department of Gastroenterology, The Tenth Hospital Affiliated to Tongji University, Shanghai 200072, P.R. China.
authors.forename: Ying-Qun
authors.initials: YQ
authors.lastname: Zhou
authors.affiliation: Institute of Oncology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.
authors.forename: Feng-Hou
authors.initials: FH
authors.lastname: Gao
mesh_terms: D051926:Basigin / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009578:Nitrobenzenes / Q000494:pharmacology* / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology*; D011725:Pyridines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D009578:Nitrobenzenes; D011725:Pyridines; D034741:RNA, Small Interfering; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051926:Basigin; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; C093642:SB 203580