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Abstract Title:

β-Elemene inhibits the metastasis of multidrug-resistant gastric cancer cells through miR-1323/Cbl-b/EGFR pathway.

Abstract Source:

Phytomedicine. 2020 Feb 10 ;69:153184. Epub 2020 Feb 10. PMID: 32199253

Abstract Author(s):

Mingming Deng, Bofang Liu, Huicong Song, Ruoxi Yu, Dan Zou, Yang Chen, Yanju Ma, Fei Lv, Ling Xu, Zhe Zhang, Qingjie Lv, Xianghong Yang, Xiaofang Che, Xiujuan Qu, Yunpeng Liu, Ye Zhang, Xuejun Hu

Article Affiliation:

Mingming Deng

Abstract:

BACKGROUND: β-Elemene is a natural agent extracted from the traditional Chinese herbal medicine Curcuma wenyujin that is a promising novel plant-derived drug with broad-spectrum anticancer activity. Our previous study identified an enhanced capacity for metastasis in multidrug resistant (MDR) gastric cancer and breast cancer cells. However, the anti-metastatic effects of β-Elemene on MDR cancer cells remain unknown.

PURPOSE: In this study, we posit the hypothesis thatβ-elemene possesses antimetastatic effects on MDR cancer cells.

METHODS: Cell viability assay was used to assess the resistance of SGC7901/ADR cells and the cytotoxic effects ofβ-Elemene. Wound healing, transwell assay and lung metastatic mice model were used to the anti-metastasis effects of β-Elemene. MicroRNA microarray analysis was used to explore potential regulated miRNAs. Luciferase reporter assay was used to identify the direct target. Human MMP antibody array, western blot, immunoprecipitation, qRT-PCR analyses and immunohistochemistry were conducted to investigate the underlying anti-metastasis mechanism of β-Elemene.

RESULTS: In this study, we found thatβ-Elemene significantly inhibited the metastatic capacity of MDR gastric cells in vivo and in vitro. Mechanistically, we found that β-Elemene regulated MMP-2/9 expression and reversed epithelial-mesenchymal transition. Further studies showed that β-Elemene upregulated Cbl-b expression, resultingin inhibition of the EGFR-ERK/AKT pathways, which regulate MMP-2/9. Additionally, we confirmed that β-Elemene upregulated Cbl-b by inhibiting miR-1323 expression. Finally, we found that numbers of metastatic tumor nodules were significantly decreased in the lungs of nude mice after β-Elemene treatment.

CONCLUSION: Our results suggested thatβ-Elemene inhibits the metastasis of MDR gastric cancer cells by modulating the miR-1323/Cbl-b/EGFR signaling axis.

Study Type : Animal Study, In Vitro Study

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Sayer Ji
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