Effects Of Stromal Interaction Molecular1Gene On Prostate Cancer Cell Migration And Invasion And Epithelial-mesenchymal Transition

Background and Objective: Stormal interaction molecule1(STIM1) isoverexpressed in various tumor tissues, and participated in tumor growth, cancerangiogenesis and metastasis. Our previous studies have showed that, STIM1expression was increased in prostate cancer, and was correlated with the stage of prostatecancer. Inhibiting the expression of STIM1in prostate cancer PC-3cells could decreasecancer cell proliferation and induce cell apoptosis. Our objective was to observe the effectof STIM1on cell migration and invasion in prostate cancer DU145and PC-3cells, and toexplore whether STIM1contribute to reverse the epithelial-mesenchymal transition (EMT)transformation in DU145cells.Methods: DU145and PC-3cells were transfected with lentiviral vectorSTIM1-pGCSIL-GFP which carrying STIM1shRNA (si-STIM1group) and negativevector (NC group), normal DU145and PC-3cells without any interference were used asbank control (Mock group).72h after transfection, the expression of STIM1in DU145andPC-3cells was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) andwestern blot. The cell mobility, migration and invasion ability of DU145and PC-3cellswere measured by wound-healing assay and transwell migration and invasion assaysrespectively. The expression of EMT markers (E-cadherin, N-cadherin, vimentin, α-SMA)in DU145cells was detected by semi-quantitative RT-PCR and western blot analysis.Results:72h after the transfection, the transfection efficiency was greater than80%,and MOI was20. As it was compared with NC group, the inhibition rate of STIM1inmRNA and protein levels in si-STIM1group were72%and64%in DU145cellsrespectively, and they were81%and85%in PC-3cells respectively. Both had statisticaldifferences (P <0.05). The wound-healing assay showed cell mobility in si-STIM1group was significantly decreased. In DU145cells, the number of migrated cellsin group Mock, NC and si-STIM1was87.2±7.3,85.4±8.5,45.6±4.3respectively. Thenumber of invaded cells was96.6±9.3,99.1±10.4,52.6±6.7respectively. In PC-3cells,the number of migrated cells in group Mock, NC and si-STIM1was61.8±3.3,58.4±6.2,34.1±6.3respectively. The number of invaded cells was32.4±4.6,35.1±3.9,19.3±3.2respectively. These indicated that the ability of cell migration and invasion weredecreased after STIM1was inhibited in prostate cancer cells (P<0.05). When DU145cellswas transfected with STIM1shRNA, its epithelial marker E-cadherin increased in bothmRNA and protein levels (1.81and3.81fold respectively), its mesenchymal markersN-cadherin decreased in both mRNA and protein levels (0.44and0.69fold respectively),and both Vimentin and α-SMA were also decreased (P<0.05).Conclusions:1. The expression of STIM1in prostate cancer cell line DU145,PC-3cells iscorrelated with its cell mobility, cell migration and cell invasion ability;2. When STIM1was inhibited in DU145cells, the epithelial marker E-cadherinincreased, mesenchymal markers N-cadherin, Vimentin and α-SMA were obviouslydecreased in both mRNA and protein levels;3. The mechanism why STIM1could inhibit prostate cancer DU145metastasis maybe associated with the ability of STIM1inhibition can reverse the EMT in prostate cancercells.