Pcdh10Gene Inhibits Migration And Invasion Ability Of Multiple Myeloma Cells And Its Related Mechanisms

Objective PCDH10(Protocadherin-10) belongs to the protocadherinsuper-family, locating in4q28.3. PCDH10has been identified as a tumorsuppressor gene (TSG). PCDH10gene might contribute to the inhibitionfunction of tumor cells growth, migration, invasion and angiogenesis.Multiple myeloma (MM) is a plasma cell tumor. PI3K/AKT activationplays an important role in MM growing process. Our previous study showsthat PCDH10gene suppresses the MM cell lines growing. However atpresent, the molecular mechanism of development of MM is not fully clear.The ultimate goal of this study is to investigate the activity of PCDH10signal transduction pathways and whether PCDH10affect the invasion,migration ability and angiogenesis of MM cells.Methods The human MM cell lines RPMI8226cells and KM3cellswere transfected with liposome vector pcDNA3.1(+)PCDH10andpcDNA3.1(+) plasmid respectively; The following experiments,untransfected, pcDNA3.1(+) plasmid transfected cells and untreatmentcells were used as control. We determined the expression level of PCDH10by real-time PCR and western blot. Transwell assay was used to observe the cell invasion and migration ability. Tube formation method wasemployed to investigate angiogenesis. The related proteins expression ofPI3K，AKT，p-AKT，p70S6K，mTOR，MMPs，cyclinD1and VEGFwere determined by western blot.Results After transfection with PCDH10, the expression level ofPCDH10gene and protein were significantly upregulated. MTT showedthat PCDH10could inhibit the proliferation of MM cells. Transwell assayshowed that invasion and migration ability significantly decreased whenPCDH10gene expressed in MM cell lines(P<0.05). Tube formation methodrevealed that angiogenesis dereasing (P<0.05). MM cell lines withPCDH10gene expressed resulted in down-regulation the expression ofPI3K、AKT、p-AKT、p70S6K、mTOR、MMPs、cyclinD1and VEGF(P<0.05).