Mesenchymal stem cells facilitate gastric cancer cell growth and oxaliplatin resista nce via upregulation of SMARCA5

Abstract

Purpose: To evaluate the role of mesenchymal stem cells (MSCs) in gastric cancer (GC), and reveal its underlying mechanisms.
 Methods: Expression of SMARCA5 was quantified in GES-1, AGS and MKN45 cell lines. In MSCs-GC co-cultured cells, cell viability was assessed using cell counting kit-8 (CCK-8) assay, and colony formation were performed to determine cell proliferation. The invasion of the MSCs-GC cells was evaluated by Transwell assay. The levels of vimentin, snail and slug, as well as Wingless-Int (Wnt)/β-catenin related proteins β-catenin, Axin, c-myc, and matrix metalloproteinase (MMP)-7 were determined using immunoblotting. Oxaliplatin was added to GC cells, and the effect of siSMARCA5 on cell sensitivity to oxaliplatin was investigated after transfection with SMARCA5 siRNA into MSCs-GC cells.
 Results: SMARCA5 was highly expressed after co-culture with MSCs (p < 0.001). The MSCs facilitated the proliferation of GC cells, and enhanced cell invasion as well as migration (p < 0.001) compared with untreated cells. MSCs also promoted epithelial–mesenchymal transition (EMT) by increasing production of vimentin, snail, and slug (p < 0.001). The MSCs decreased the sensitivity of GC cells to oxaliplatin, while the knockdown of SMARCA5 reversed the effect (p < 0.001). Furthermore, MSCs up-regulated β-catenin, c-myc, and MMP-7 levels, but downregulated Axin expression compared with untreated cells (p < 0.001). However, siSMARCA5 blocked these processes compared with si-NC group (p < 0.001).
 Conclusion: MSCs facilitate GC cell growth and oxaliplatin resistance by upregulating SMARCA5 and activating Wnt/β-catenin signaling. This may provide an alternative treatment target for patients with GC.