Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

Yongli Nie¹, Jun Guo², Jun Chen³, Yanyan Wang⁴

¹Department of Oncology, Sinopharm Han Jiang Hospital, Shiyan, Hubei Province, China; ²Department of Oncology, Hubei University of Medicine, Shiyan, Hubei Province, 442700, China; ³Experimental Center, Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Shiyan, Hubei Province, 442700, China; ⁴Department of MR/CT, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi Province, 030013, China.

For correspondence:- Yanyan Wang Email: yanyan_w12@163.com Tel:+863514650090

Accepted: 23 January 2023 Published: 27 February 2023

Citation: Nie Y, Guo J, Chen J, Wang Y. Mesenchymal stem cells facilitate gastric cancer cell growth and oxaliplatin resistance via upregulation of SMARCA5. Trop J Pharm Res 2023; 22(2):253-260 doi: 10.4314/tjpr.v22i2.5

© 2023 The authors.
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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.

Keywords: Mesenchymal stem cells, Gastric cancer, SMARCA5, Wingless Int/Î²-catenin