Abstract
The traditional herb medicine Ferula sinkiangensis K. M. Shen (F. sinkiangensis) has been used to treat stomach disorders in Xinjiang District for centuries. Umbelliprenin is the effective component isolated from F. sinkiangensis which is particularly found in plants of the family Ferula. We previously reported the promising effects of Umbelliprenin against gastric cancer cells, but its anti-migration effect remained unknown. Here we investigated the anti-migration effect and mechanism of Umbelliprenin in human gastric cancer cells. In SRB assay, Umbelliprenin showed cytotoxic activities in the gastric cancer cell lines AGS and BGC-823 in a dose-and-time-dependent manner, while it showed lower cytotoxic activity in the normal gastric epithelium cell line GES-1. During transwell, scratch and colony assays, the migration of tumor cells was inhibited by Umbelliprenin treatment. In gelatin zymography assay, Umbelliprenin could inhibit the expression of MMP2 and MMP9 in tumor cells The expression levels of the Wnt-associated signaling pathway proteins were analyzed with western blots, and the results showed that Umbelliprenin decreased the expression levels of proteins of the Wnt signalling pathway, such as Wnt-2, β-catenin, GSK-3β, p-GSK-3β, Survivin and c-myc. The translocation of β-catenin to the nucleus was also inhibited by Umbelliprenin treatment. In TCF reporter assay, the transcriptional activity of T-cell factor/lymphoid enhancer factor (TCF/LEF) was decreased after Umbelliprenin treatment. The in vivo results suggested that Umbelliprenin induced little to no harm in the lung, heart and kidney. Overall, these data provided evidence that Umbelliprenin may inhibit the growth, invasion and migration of gastric cancer cells by disturbing the Wnt signaling pathway.
Highlights
Gastric cancer is the fourth most common cancer worldwide and is one of the most prevalent cancers among men in China [Kim et al, 2015; Zheng et al, 2016], which may be related to their preference for pickled food and red meat [Zeng et al, 2015].The clinical outcome of gastrointestinal cancer surgery is limited because of the high rates of postoperative complications, such as the systemic inflammatory response [Climent et al, 2015], which may increase tumor recurrence after surgery [Bohle et al., 2010]
Because Umbelliprenin appeared to be most effective in gastric cancer cells among other common cancer cells, we studied its anti-proliferative effects in the two human gastric cancer cell lines: AGS and BGC-823 as well as in the human gastric epithelial cell line GES-1
The results showed that Umbelliprenin inhibited the growth in both the AGS and BGC-823 gastric cancer cell lines with an IC50 of
Summary
The clinical outcome of gastrointestinal cancer surgery is limited because of the high rates of postoperative complications, such as the systemic inflammatory response [Climent et al, 2015], which may increase tumor recurrence after surgery [Bohle et al., 2010]. Studies have focused on raising the overall survival rate for gastric cancer [Cho et al, 2016]. Only trastuzumab and ramucirumab have been approved for the treatment of advanced gastric cancer as targeted monoclonal antibodies [Roviello et al, 2016], suggesting that less toxic and more effective therapeutic options are necessary. Metastasis is the main cause of death in cancer patients [Tang et al, 2014]. The invasion of cancer cells is affected and modulated by many biological molecules and signaling pathways.
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