Mesenchymal stem cells facilitate gastric cancer cell growth and oxaliplatin resista nce via upregulation of SMARCA5
| Autor: | Nie, Yongli, Guo, Jun, Chen, Jun, Wang, Yanyan |
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| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Tropical Journal of Pharmaceutical Research; Vol. 22 No. 2 (2023); 253-260 |
| ISSN: | 1596-5996 1596-9827 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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