The tumor microenvironment (TM) is an essential factor of tumor progression. Mesenchymal stem cells (MSCs) are important components of the TM and play critical roles in cancer metastasis. Resveratrol (RES) is a potential antitumor drug that has attracted extensive attention. However, it remains unclear whether RES can exert its antitumor activity by targeting MSCs located in the TM. In this study, we demonstrated that the conditioned medium of gastric-cancer-derived MSCs (GC–MSCs) promoted gastric cancer (GC) metastasis and facilitated the progression of epithelialmesenchymal transition (EMT) of GC cells. However, after pretreatment with RES, the prometastatic effect of GC–MSCs on GC cells was reversed. Furthermore, RES reduced GC–MSC (IL-6, IL-8, MCP-1, VEGF) gene expression and protein secretion, and counteracted the activation of the GC–MSC-induced Wnt/β-catenin signaling of GC cells, with less β-catenin nuclear transport and declined expression of β-catenin, CD44, and CyclinD3 in GC cells. Re-expression of β-catenin impaired the inhibitory effect of RES on GC cells. In conclusion, RES restricted the mobility increase of GC cells and reversed the progress of EMT induced by GC–MSCs by inactivating the Wnt/β-catenin signaling. GC–MSCs are promising target for RES in the inhibition of GC metastasis.

中文翻译：

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胃癌来源的间充质干细胞：白藜芦醇有望抑制胃癌转移。

肿瘤微环境（TM）是肿瘤进展的重要因素。间充质干细胞（MSCs）是TM的重要组成部分，在癌症转移中起关键作用。白藜芦醇（RES）是一种潜在的抗肿瘤药物，已引起广泛关注。但是，尚不清楚RES是否可以通过靶向位于TM中的MSC来发挥其抗肿瘤活性。在这项研究中，我们证明了胃癌衍生的MSCs（GC–MSCs）的条件培养基可促进胃癌（GC）转移并促进GC细胞的上皮间质转化（EMT）的进程。但是，用RES预处理后，GC–MSC对GC细胞的前转移作用被逆转。此外，RES降低了GC–MSC（IL-6，IL-8，MCP-1，VEGF）的基因表达和蛋白质分泌，并抵消了GC–MSC诱导的GC细胞Wnt /β-catenin信号转导的激活，减少了β-catenin核转运，并降低了GC细胞中β-catenin，CD44和CyclinD3的表达。β-catenin的重新表达削弱了RES对GC细胞的抑制作用。总之，RES通过失活Wnt /β-catenin信号传导，限制了GC细胞的迁移性增加，并逆转了由GC–MSC诱导的EMT进展。GC–MSCs有望成为RES抑制GC转移的靶标。RES通过失活Wnt /β-catenin信号传导，限制了GC细胞的迁移性增加，并逆转了由GC–MSC诱导的EMT进程。GC–MSCs有望成为RES抑制GC转移的靶标。RES通过失活Wnt /β-catenin信号传导，限制了GC细胞的迁移性增加，并逆转了由GC–MSC诱导的EMT进程。GC–MSC是RES有望抑制RES转移的靶标。