The Effect of Dihydroartemisinin on the Malignancy and Epithelial-Mesenchymal Transition of Gastric Cancer Cells

被引:25
作者
Li, Nan [1 ]
Zhang, Suyun [2 ]
Luo, Qiong [2 ]
Yuan, Fang [3 ]
Feng, Rui [2 ]
Chen, Xiangqi [3 ]
Yang, Sheng [2 ]
机构
[1] Fujian Med Univ, Dept Chinese Med, Union Hosp, Fuzhou 350001, Fujian, Peoples R China
[2] Fujian Med Univ, Dept Oncol, Union Hosp, Fuzhou 350001, Fujian, Peoples R China
[3] Fujian Med Univ, Resp Med, Union Hosp, Fuzhou 350001, Fujian, Peoples R China
关键词
Dihydroartemisinin; gastric cancer cells; malignant behavior; epithelial-mesenchymal transition; cell counting kit-8 (CCK-8); cell invasion assay; IN-VITRO; GROWTH; EMT; VIABILITY; APOPTOSIS; PROTEINS; SNAIL;
D O I
10.2174/1389201020666190611124644
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Objective: This study aimed to observe the effects of dihydroartemisinin (DHA) on the proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (EMT) of the human gastric cancer cell line SGC7901 cultured in vitro. Methods: We applied varying concentrations of DHA to SGC7901 cells. Cell proliferation was measured using the cell counting kit-8 (CCK-8). Flow cytometry, Transwell invasion assay, and cell scratch assay were used to investigate the cell's apoptosis, invasion, and migration. Western blot was used to assess the expression levels of EMT markers E-cadhein and Vimentin, protein kinases Akt and phosphorylated AKT (p-AKT), and the cell transcription factor Snail. Results: DHA can effectively inhibit the malignant proliferation of gastric cancer cells in a time- and dose-dependent manner. In this study, with longer incubation times and increased drug concentrations, the antiproliferation effect of DHA on SGC7901 cells increased gradually (P<0.05). In addition, with the increase of drug concentration, the expression levels of E-cadhein, an epithelial-mesenchymal transition marker, remarkably increased, whereas the protein expression levels of the mesenchymal markers Vimentin, Akt, p-Akt, and Snail significantly decreased (P<0.05). Conclusion: DHA can effectively inhibit the proliferation, invasion, and metastasis of the gastric cancer cell line SGC7901 and induce cancer cell apoptosis. DHA can also downregulate PI3IC/AKT and Snail activities and inhibit the epithelial-mesenchymal transition of gastric cancer cells. The potential anticancer effects of DHA deserve further investigation.
引用
收藏
页码:719 / 726
页数:8
相关论文
共 25 条
[1]   Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence [J].
Ansieau, Stephane ;
Bastid, Jeremy ;
Doreau, Agnes ;
Morel, Anne-Pierre ;
Bouchet, Benjamin P. ;
Thomas, Clemence ;
Fauvet, Frederique ;
Puisieux, Isabelle ;
Doglioni, Claudio ;
Piccinin, Sara ;
Maestro, Roberta ;
Voeltzel, Thibault ;
Selmi, Abdelkader ;
Valsesia-Wittmann, Sandrine ;
de Fromentel, Claude Caron ;
Puisieux, Alain .
CANCER CELL, 2008, 14 (01) :79-89
[2]   Epigenetic plasticity: A central regulator of epithelial-to-mesenchymal transition in cancer [J].
Bedi, Upasana ;
Mishra, Vivek Kumar ;
Wasilewski, David ;
Scheel, Christina ;
Johnsen, Steven A. .
ONCOTARGET, 2014, 5 (08) :2016-2029
[3]   Dihydroartemisinin inhibits growth of pancreatic cancer cells in vitro and in vivo [J].
Chen, Hua ;
Sun, Bei ;
Pan, Shangha ;
Jiang, Hongchi ;
Sun, Xueying .
ANTI-CANCER DRUGS, 2009, 20 (02) :131-140
[4]   Cancer Statistics in China, 2015 [J].
Chen, Wanqing ;
Zheng, Rongshou ;
Baade, Peter D. ;
Zhang, Siwei ;
Zeng, Hongmei ;
Bray, Freddie ;
Jemal, Ahmedin ;
Yu, Xue Qin ;
He, Jie .
CA-A CANCER JOURNAL FOR CLINICIANS, 2016, 66 (02) :115-132
[5]   Gastric cancer: Current status of lymph node dissection [J].
Degiuli, Maurizio ;
De Manzoni, Giovanni ;
Di Leo, Alberto ;
D'Ugo, Domenico ;
Galasso, Erica ;
Marrelli, Daniele ;
Petrioli, Roberto ;
Polom, Karol ;
Roviello, Franco ;
Santullo, Francesco ;
Morino, Mario .
WORLD JOURNAL OF GASTROENTEROLOGY, 2016, 22 (10) :2875-2893
[6]   Dihydroartemisinin targets VEGFR2 via the NF-κB pathway in endothelial cells to inhibit angiogenesis [J].
Dong, Fengyun ;
Zhou, Xia ;
Li, Changsheng ;
Yan, Suhua ;
Deng, Xianming ;
Cao, Zhiqun ;
Li, Liqun ;
Tang, Bo ;
Allen, Thaddeus D. ;
Liu, Ju .
CANCER BIOLOGY & THERAPY, 2014, 15 (11) :1479-1488
[7]   EPITHELIA SUSPENDED IN COLLAGEN GELS CAN LOSE POLARITY AND EXPRESS CHARACTERISTICS OF MIGRATING MESENCHYMAL CELLS [J].
GREENBURG, G ;
HAY, ED .
JOURNAL OF CELL BIOLOGY, 1982, 95 (01) :333-339
[8]   Inhibition of Akt activity induces the mesenchymal-to-epithelial reverting transition with restoring E-cadherin expression in KB and KOSCC-25B oral squamous cell carcinoma cells [J].
Hong, Kyoung-Ok ;
Kim, Ji-Hong ;
Hong, Ji-Soo ;
Yoon, Hye-Jung ;
Lee, Jae-Il ;
Hong, Sam-Pyo ;
Hong, Seong-Doo .
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2009, 28
[9]   Suppression of PMA-induced tumor cell invasion by dihydroartemisinin via inhibition of PKCα/Raf/MAPKs and NF-κB/AP-1-dependent mechanisms [J].
Hwang, Yong Pil ;
Yun, Hyo Jeong ;
Kim, Hyung Gyun ;
Han, Eun Hee ;
Lee, Gye Won ;
Jeong, Hye Gwang .
BIOCHEMICAL PHARMACOLOGY, 2010, 79 (12) :1714-1726
[10]   BMP2 accelerates the motility and invasiveness of gastric cancer cells via activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway [J].
Kang, Myoung Hee ;
Kim, Jun Suk ;
Seo, Ji Eun ;
Oh, Sang Cheul ;
Yoo, Young A. .
EXPERIMENTAL CELL RESEARCH, 2010, 316 (01) :24-37