title: Arsenic trioxide inhibits invasion/migration in SGC-7901 cells by activating the reactive oxygen species-dependent cyclooxygenase-2/matrix metalloproteinase-2 pathway.
abstract: Arsenic trioxide (As(2)O(3)) has been shown to inhibit invasion/migration in cancer cells. However, the underlying mechanism is poorly understood. To identify the role of As(2)O(3) in regulating invasion/migration activity in human gastric cancer SGC-7901 cells, the effects of As(2)O(3) on cell invasion/migration activity, the expression of cyclooxygenase-2 (Cox-2), prostaglandin E2 (PGE2), thromboxane B2 (TXB2), leukotriene B4 (LTB4), and matrix metalloproteinase-2 (MMP-2) and intracellular reactive oxygen species (ROS) were examined. Furthermore, N-acetyl-l-cysteine (NAC, a radical scavenger) and celecoxib (a Cox-2 inhibitor) were used to explore the molecular mechanism. The results demonstrated that As(2)O(3) (1 and 2 μmol/L) inhibited invasion/migration activity in SGC-7901 cells at 24 h and suppressed the expression of Cox-2, PGE2 and MMP-2 (P < 0.05), whereas the same treatment had no significant effect on TXB2 and LTB4 expression. In contrast, intracellular ROS were increased (P < 0.05). Moreover, NAC eliminated the excessive ROS and restored the expression of Cox-2 and MMP-2 and invasion/migration activity in As(2)O(3)-treated cells (P < 0.05). These results suggest that ROS may be a critical factor in regulating the invasion/migration process. Moreover, celecoxib significantly decreased Cox-2, MMP-2 and PGE2 expression and inhibited invasion/migration activity in As(2)O(3)-treated cells (P < 0.05), indicating that As(2)O(3) inhibits invasion/migration by regulating the expression of Cox-2/PGE2/MMP-2. In conclusion, these results suggest that increased ROS play a critical role in inhibiting invasion/migration by suppressing the Cox-2/MMP-2 pathway in As(2)O(3)-treated SGC-7901 cells and regulating intracellular ROS levels may be a promising strategy in gastric cancer therapy.
authors.affiliation: Key Laboratory of Arid and Grassland Ecology, Ministry of Education/Arid Laboratory, School of Life Sciences, Lanzhou University, China.
authors.forename: Yingxia
authors.initials: Y
authors.lastname: Liu
authors.forename: Wenya
authors.initials: W
authors.lastname: Zhang
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Zhang
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Qi
authors.forename: Dejun
authors.initials: D
authors.lastname: Huang
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010087:Oxides / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013929:Thromboxane B2 / Q000378:metabolism
chemical_list: D001152:Arsenicals; D010087:Oxides; D017382:Reactive Oxygen Species; D007975:Leukotriene B4; D013929:Thromboxane B2; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D015232:Dinoprostone; D000077237:Arsenic Trioxide