Lysophosphatidic acid (LPA), a simple water-soluble glycerophospholipid with growth factor-like activity, regulates certain behaviors of multiple cancer types by binding to its receptor, LPA receptor 2 (LPA2). Notch1 is a key mediator in multiple human cancer cell types. The association between LPA2 and Notch1 in gastric cancer cells is not well known. The present study aimed to investigate the function of LPA2 and Notch1 in controlling the migration and invasion activities of SGC-7901 gastric cancer cells following stimulation with LPA. It was revealed that LPA may stimulate the expression of Notch1 and Hes family bHLH transcription factor 1, and the phosphorylation of protein kinase B which belongs to the Notch pathway. Furthermore, by performing transwell migration and invasion assays, immunofluorescent staining, analyzing the expression of markers for the epithelial-mesenchymal transition (EMT) and downregulating LPA2 and Notch1 expression, it was verified that LPA2 and Notch1 mediated the metastasis, invasion, EMT and rebuilding of the cytoskeleton of SGC-7901 cells upon LPA treatment. An immunoprecipitation assay revealed that LPA2 interacted with Notch1 in SGC-7901 cells. The present study may provide novel ideas and an experimental basis for identifying the factors that affect the functions of SGC-7901 cells.
The function of curcumin on the gastric cancer cell line, SGC-7901 is unknown. The present study aimed to observe the effects of curcumin on gastric cancer cells through the Shh and Wnt signaling pathways. Methods: SGC-7901 cells were transfected with si-Gli1 and si-β-catenin siRNA, then cells were stimulated with curcumin and its effects on cell migration, invasion, cytoskeleton remodeling, EMT, apoptosis and cell cycle were investigated by transwell assays, immunofluorescence and flow cytometry assays. The interaction between Gli1 and β-catenin was observed by co-immunoprecipitation. Results: We show that curcumin suppressed the expression of Shh, Gli1 and Foxm1 in the Shh signaling pathway, and the expression of β-catenin in the Wnt signaling pathway in SGC-7901 cells, both in mRNA and protein. As a result, cellular migration, invasion and cytoskeletal remodeling ability decreased. Our results revealed that when stimulated with curcumin, cells showed decreased cellular migration and invasion, while enhanced apoptosis. In addition, curcumin induced cytoskeletal remodeling and S phase cell cycle arrest. The inhibition of Shh and Wnt signaling pathway and the addition of curcumin also inhibited the epithelial-mesenchymal transition process. Furthermore, a physical interaction was observed between Gli1 of the Shh signaling and β-catenin of the Wnt signaling in these cells, but curcumin inhibited the interaction of these two proteins. Conclusion:The present study indicated that curcumin plays an anti-tumor role through Gli1-β-catenin pathway in gastric cancer SGC-7901 cells.
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