Effects of siRNA-mediated silencing of myeloid cell leukelia-1 on the biological behaviors and drug resistance of gastric cancer cells.

Objective: This study was to investigate the effects of siRNA mediated silencing of myeloid cell leukelia-1 (Mc1-1) on the biological behaviors and drug resistance of human drug-resistant gastric cancer (GC) cell lines, and to explore the potential mechanisms. Methods: siRNA targeting Mcl-1 mRNA were designed and independently transfected into SGC-7901/VCR and SGC-7901/DDP. Cell proliferation and drug sensitivity were examined by MIT assay. Cell apoptosis and cell cycle were detected by flow cytometry. Cell Invasion and migration abilities were detected by transwell chamber assays. The expressions of drug-resistance-related genes and apoptosis-related proteins were detected by quantitative real-time PCR and Western blot assay, respectively. Results: siRNA effectively inhibited the Mcl-1 expression, lowered the proliferation rate (P<0.05), raised the apoptosis rate (P<0.05), and arrested cells in S-phase (P<0.05). After inhibiting Mcl-1, the cell migration and invasion decreased (P<0.05), the resistance to VCR, DDP and 5-Fu was reversed to different extents (P<0.05), TS mRNA expression increased significantly (P<0.05), MDR1 remained unchanged (P>0.05), but DPD and TOP2A decreased significantly (P<0.05). Following Mcl-1 silencing, BcI-2 was over-expressed in VCR-siRNA group, but the expressions of Fas and survivin reduced markedly (P<0.05); BcI-2 and Fas expressions decreased significantly in DDP-siRNA group (P<0.05), but survivin expression remained unchanged. Conclusion: McI-1 is implicated in the proliferation, invasion, apoptosis and drug resistance of GC cells, and may be a promising target for the therapy of GC.