Abstract
Background: CXCR7 is overexpressed in a variety of cancer and is known to promote cell migration, invasion and metastasis. Therefore, inhibition of CXCR7 can prevent tumor progression. In this study, we investigated the role of decursin on the CXCR7 expression and its antitumor effects in gastric cancer.
Methods: CXCR7-overexpressing gastric cell lines were established, and the expression of membrane CXCR7 was confirmed by flow cytometry and immunocytochemistry. Cell viability and anoikis assay were performed using CCK-8 reagent. The effect of decursin on cell migration and invasion was tested using transwell system, and the cleavage of PARP and caspase-3 was performed in western blotting and was confirmed by flow cytometry using apoptosis detection kit. The inhibition of tumor growth by decursin was also demonstrated in vivo by measuring tumor growth using subcutaneous injection mouse model.
Results: CXCR7 overexpression significantly increased the invasion and migration, and tumor growth in gastric cancer cells. Administration of decursin decreased the membrane expression of CXCR7 in a concentration dependent manner and significantly inhibited tumor progression by suppressing cell migration, invasion and proliferation. In addition, decursin treatment impeded in vivo tumor growth in BALB/c nude mice. CXCR7-induced STAT3 and c-Myc activation were inhibited by decursin, whereas pro-apoptotic pathway was activated.
Conclusion: Decursin inhibited the cell growth, migration and invasion via downregulating the membrane expression of CXCR7 in gastric cancer in vitro and suppressed tumor growth in vivo suggesting that decursin might be used as a therapeutic agent alone or in combination with other anticancer agents in gastric cancer.
Citation Format: Solbi Kim, Nayoung Kim, Mina Joo, HueungJin Jeon, Hyewon Ryu, Hyo Jin Lee. Decursin inhibits tumor growth, migration and invasion through the regulation of CXCR7 expression in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3866.
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