title: Suppression of cell invasion and migration by propofol are involved in down-regulating matrix metalloproteinase-2 and p38 MAPK signaling in A549 human lung adenocarcinoma epithelial cells.
abstract: Metastasis is a major cause of death of patients with malignant tumors. Matrix metalloproteinases (MMPs) are important for the migration and invasion of various types of cancer cell. Propofol is a known anesthetic agent, widely used for short-term anesthesia and for longer-term sedation. Propofol inhibits the proliferation of a variety of tumor cells, but there is no available information regarding propofol-inhibited migration and invasion of tumor cells in vitro. In this study, we investigated the effects of propofol on the migration and invasion of human lung carcinoma A549 cells. Wound healing assay and Boyden chamber assays indicated that propofol inhibited the migration and invasion of A549 cells in vitro. Gelatin zymographic analysis showed the inhibitory effect of propofol on the activation of expression MMP-2. Western blot analysis also indicated that propofol suppressed the protein expiration of growth factor receptor-bound protein 2 (GRB2), Jun N-terminal kinases 1/2 (p-JNK1/2), p-p38, MMP-2 and MMP-9 in A549 cells. Results from real-time PCR assay also showed that propofol inhibited the mRNA gene expression of MMP-2, -7 and -9, and enhanced that of tissue inhibitor of metalloproteinase 1 (TIMP1) and TIMP2 in A549 cells. Taken together, these data show that propofol inhibits MMP-2 and -9 mRNA and protein expressions, resulting in suppression of lung cancer cell invasion and migration in vitro.
authors.affiliation: Department of Anesthesiology, E-DA Hospital/I-Shou University, Kaohsiung, Taiwan, ROC.
authors.forename: King-Chuen
authors.initials: KC
authors.lastname: Wu
authors.forename: Su-Tso
authors.initials: ST
authors.lastname: Yang
authors.forename: Te-Chun
authors.initials: TC
authors.lastname: Hsia
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
authors.forename: Shang-Ming
authors.initials: SM
authors.lastname: Chiou
authors.forename: Chi-Cheng
authors.initials: CC
authors.lastname: Lu
authors.forename: Rick Sai-Chuen
authors.initials: RS
authors.lastname: Wu
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D015742:Propofol / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D015742:Propofol