title: Knockdown of c-Met inhibits cell proliferation and invasion and increases chemosensitivity to doxorubicin in human multiple myeloma U266 cells in vitro.
abstract: c-Met, a receptor tyrosine kinase and its ligand, hepatocyte growth factor, are critical in cellular proliferation, motility and invasion and confer resistance to specific chemotherapeutic drugs. However, little is known about the impact of c-Met knockdown on the biological functions of human multiple myeloma U266 cells. The present study was designed to determine the role of c-Met in the proliferation and invasion of U266 cells, using RNA interference technology in vitro. In our study, the c-Met short hairpin RNA (shRNA) was successfully transfected into U266 cells, which resulted in the significant inhibition of transcription and expression of c-Met. The down-regulation of c-Met inhibited the proliferation potential, adherence and invasiveness of U266 cells, and also increased chemosensitivity to doxorubicin. The c-Met shRNA in U266 cells induced apoptosis and increased the accumulation of cleavage PARP and cleavage caspase-3. However, the expression of Bcl-2 and Bax did not change following the c-Met knockdown. Taken together, our data reveal that the down-regulation of c-Met inhibits proliferation and invasion and increases the chemosensitivity of U266 cells. Thus, the targeting of c-Met could be an effective therapeutic approach against multiple myeloma.
authors.affiliation: Department of Hematology and Rheumatology, The First Affiliated Hospital of Fujian Medical University, Fujian, P.R. China.
authors.forename: Wenzhong
authors.initials: W
authors.lastname: Que
authors.forename: Junmin
authors.initials: J
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D004317:Doxorubicin; D019859:Proto-Oncogene Proteins c-met