单位：[a]Department of Respiratory and Infectious Disease of Geriatrics, the First Hospital of China Medical University, Shenyang 110001, China[b]Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China[c]The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang 110001, China[d]Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, China[e]Department of Pathology, Shengjing Hospital of China Medical University, Shenyang 110001, China中国医科大学附属盛京医院[f]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China[g]Graduate School of Peking Union Medical College, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100005, China[h]Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, Zhejiang, China
Background: beta-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 beta-Elemene on MDR cancer cells remain unknown. Purpose: In this study, we posit the hypothesis that beta-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 of beta-Elemene. Wound healing, transwell assay and lung metastatic mice model were used to the anti-metastasis effects of beta-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 beta-Elemene. Results: In this study, we found that beta-Elemene significantly inhibited the metastatic capacity of MDR gastric cells in vivo and in vitro. Mechanistically, we found that beta-Elemene regulated MMP-2/9 expression and reversed epithelial-mesenchymal transition. Further studies showed that beta-Elemene upregulated Cbl-b expression, resulting in inhibition of the EGFR-ERK/AKT pathways, which regulate MMP-2/9. Additionally, we confirmed that beta-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 beta-Elemene treatment. Conclusion: Our results suggested that beta-Elemene inhibits the metastasis of MDR gastric cancer cells by modulating the miR-1323/Cbl-b/EGFR signaling axis.
基金：
National Science and Technology Major Project of the Ministry of Science and Technology of China [2017ZX09304025]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81472193, 81972197]; Science and Technology Plan Project of Liaoning Province [2016007010]; Key Research and Development Program of Shenyang [17-230-9-01]
第一作者单位：[a]Department of Respiratory and Infectious Disease of Geriatrics, the First Hospital of China Medical University, Shenyang 110001, China[f]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China[g]Graduate School of Peking Union Medical College, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100005, China
共同第一作者：
通讯作者：
通讯机构：[a]Department of Respiratory and Infectious Disease of Geriatrics, the First Hospital of China Medical University, Shenyang 110001, China[c]The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang 110001, China[*a]Department of Respiratory and Infectious Disease of Geriatrics, the First Hospital of China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang 110001, China[*b]the First Laboratory of Cancer Institute, the First Hospital of China Medical University, No. 155 North Nanjing Street, Heping District, Shenyang, 110001, China
推荐引用方式(GB/T 7714)：
Deng M,Liu B,Song H,et al.beta-Elemene inhibits the metastasis of multidrug-resistant gastric cancer cells through miR-1323/Cbl-b/EGFR pathway[J].PHYTOMEDICINE.2020,69:doi:10.1016/j.phymed.2020.153184.
APA：
Deng, M,Liu, B,Song, H,Yu, R,Zou, D...&Hu, X.(2020).beta-Elemene inhibits the metastasis of multidrug-resistant gastric cancer cells through miR-1323/Cbl-b/EGFR pathway.PHYTOMEDICINE,69,
MLA：
Deng, M,et al."beta-Elemene inhibits the metastasis of multidrug-resistant gastric cancer cells through miR-1323/Cbl-b/EGFR pathway".PHYTOMEDICINE 69.(2020)
医学