Abstract
Background: C-X-C motif chemokine receptor 7 (CXCR7) is a member of the G protein-coupled receptor family and is reported to be involved in the invasion, migration and tumor progression of various cancers. However, few compounds regulate CXCR7 expression. Therefore, compounds that negatively regulate CXCR7 may inhibit tumor progression and thus serve as candidates for effective anti-cancer drugs. In this study, we investigated the regulation of CXCR7 by decursin derived from Angelica gigas and its downstream signaling.
Methods: A CXCR7-overexpressing stable cell line was established in gastric cancer cells, and the expression of membrane CXCR7 was confirmed by flow cytometry and immunocytochemistry. Cell viability was examined using the CCK-8 assay. We investigated the potential of decursin to inhibit cell migration and invasion using a Transwell system. We also examined the mechanism of CXCR7 regulation by decursin by performing Western blot analysis of downstream proteins using phospho-specific antibodies.
Results: CXCR7 overexpression significantly increased the proliferation, invasion and migration of gastric cancer cells. In addition, spheres were well formed under anchorage-independent conditions in CXCR7-expressing gastric cancer cells. Levels of phospho-Stat3 and -Akt, positive regulators of cancer progression, were significantly increased. Decursin treatment reduced CXCR7 expression at the cellular membrane, and significantly decreased cancer cell invasion and migration. When treated with decursin, the sphere formation capacity decreased in a dose-dependent manner. In addition, decursin decreased the phosphorylation of Stat3 and its downstream target, c-Myc; however, it had no effect on Akt phosphorylation.
Conclusion: Decursin reduces the invasion, migration and tumor progression of cancer cells by inhibiting CXCR7. Decursin could be proposed as a new anti-cancer drug by decreasing the expression of CXCR7, which is believed to be a therapeutic target in gastric cancer.
Citation Format: Solbi Kim, Nayoung Kim, Hyewon Ryu, Gyu-Yong Song, Hyo Jin Lee. Decursin from Angelica gigas Nakai regulates CXCR7 expression and its downstream signaling in gastric cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2918.
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