RETRACTED: Emodin suppresses proliferation, migration and invasion in ovarian cancer cells by down regulating ILK in vitro and in vivo (Retracted Article)

被引:32
作者
Lu, Jingjing [1 ,2 ]
Xu, Ying [1 ]
Zhao, Zhe [1 ]
Ke, Xiaoning [2 ]
Wei, Xuan [1 ]
Kang, Jia [1 ]
Zong, Xuan [1 ]
Mao, Hongluan [1 ]
Liu, Peishu [1 ]
机构
[1] Shandong Univ, Qilu Hosp, Dept Obstet & Gynecol, 107 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China
[2] Handan Cent Hosp, Dept Obstet & Gynecol, Handan, Peoples R China
关键词
emodin; ILK; epithelial ovarian cancer; epithelial-mesenchymal transition; Slug; xenografts in nude mice; INTEGRIN-LINKED KINASE; EPITHELIAL-MESENCHYMAL TRANSITION; COLORECTAL-CANCER; OVEREXPRESSION; EMT; CYTOSKELETON; METASTASIS; EXPRESSION; GRADE;
D O I
10.2147/OTT.S138217
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Objective: Although our previous studies have confirmed that 1, 3, 8-trihydroxy-6-methylanthraquinone (emodin) inhibits migration and invasion in epithelial ovarian cancer (EOC) cells, the underlying molecular mechanism remains unknown. Here, the aim was to investigate the effects of emodin on EOC cells and to study further the mechanism underlying this process, both in vitro and in vivo. Materials and methods: Cell proliferation was evaluated by the methylthiazolyl tetrazolium assay. Cell migration and invasion abilities were tested using the transwell assay. The expression of integrin-linked kinase (ILK) and epithelial-mesenchymal transition (EMT)-associated factors were measured with western blotting. Results: Exogenous ILK enhanced the proliferation, migration and invasion properties of A2780 and SK-OV-3 cells. After treatment with emodin, the survival rate of cells was gradually reduced, including those of SK-OV-3/pLVX-ILK and A2780/pLVX-ILK cells, with increasing emodin concentrations. The migration and invasion abilities of A2780 and SK-OV-3 cells were effectively increased by the transfection of pLVX-ILK, which could be abrogated by following this with 48 hours of emodin treatment. Treatment with emodin significantly downregulated the expression of ILK and EMT-related proteins. So, emodin suppressed proliferation, migration and invasion in ovarian cancer cells by downregulating ILK in vitro. SK-OV-3/pLVX-Con and SK-OV-3/pLVX-ILK cells were used to generate xenografts in nude mice. Tumors grew more rapidly in the SK-OV-3/pLVX-ILK group compared with the control group, and this could be significantly inhibited by emodin. Also, the expression of E-cadherin was downregulated, while the expression of Slug, MMP-9 and Vimentin were upregulated in the SK-OV-3/pLVX-ILK group, and this could be reversed by following treatment with emodin. Emodin did not demonstrate target toxicity on hepatocytes, nephrocytes and cardiomyocytes. Conclusion: Emodin suppresses proliferation, migration and invasion in ovarian cancer by targeting ILK.
引用
收藏
页码:3579 / 3589
页数:11
相关论文
共 38 条
[1]   Cell-free 59 kDa immunoreactive integrin-linked kinase: A novel marker for ovarian carcinoma [J].
Ahmed, N ;
Oliva, K ;
Rice, GE ;
Quinn, MA .
CLINICAL CANCER RESEARCH, 2004, 10 (07) :2415-2420
[2]   Integrin-linked kinase expression increases with ovarian turnour grade and is sustained by peritoneal tumour fluid [J].
Ahmed, N ;
Riley, C ;
Oliva, K ;
Stutt, E ;
Rice, GE ;
Quinn, MA .
JOURNAL OF PATHOLOGY, 2003, 201 (02) :229-237
[3]   Integrin-linked kinase as a target for ERG-mediated invasive properties in prostate cancer models [J].
Becker-Santos, Daiana D. ;
Guo, Yubin ;
Ghaffari, Mazyar ;
Vickers, Elaine D. ;
Lehman, Melanie ;
Altamirano-Dimas, Manuel ;
Oloumi, Arusha ;
Furukawa, Junya ;
Sharma, Manju ;
Wang, Yuzhuo ;
Dedhar, Shoukat ;
Cox, Michael E. .
CARCINOGENESIS, 2012, 33 (12) :2558-2567
[4]   Promotion of epithelial-mesenchymal transition by Frizzled2 is involved in the metastasis of endometrial cancer [J].
Bian, Yiding ;
Chang, Xinwen ;
Liao, Yun ;
Wang, Jingyun ;
Li, Yiran ;
Wang, Kai ;
Wan, Xiaoping .
ONCOLOGY REPORTS, 2016, 36 (02) :803-810
[5]   Integrin-linked kinase activity modulates the pro-metastatic behavior of ovarian cancer cells [J].
Bruney, Lana ;
Liu, Yueying ;
Grisoli, Anne ;
Ravosa, Matthew J. ;
Stack, M. Sharon .
ONCOTARGET, 2016, 7 (16) :21968-21981
[6]   Overexpression of integrin-linked kinase correlates with malignant phenotype in non-small cell lung cancer and promotes lung cancer cell invasion and migration via regulating epithelial-mesenchymal transition (EMT)-related genes [J].
Chen, Donghong ;
Zhang, Yibing ;
Zhang, Xuhua ;
Li, Jing ;
Han, Bing ;
Liu, Shuo ;
Wang, Lingling ;
Ling, Yuan ;
Mao, Shitao ;
Wang, Xiaoge .
ACTA HISTOCHEMICA, 2013, 115 (02) :128-136
[7]  
Chen Ting-fang, 2008, Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, V24, P574
[8]   Emodin Ameliorates High Glucose Induced-Podocyte Epithelial-Mesenchymal Transition In-Vitro and In-Vivo [J].
Chen, Tingfang ;
Zheng, Li Yang ;
Xiao, Wenzhen ;
Gui, Dingkun ;
Wang, Xiaoxia ;
Wang, Niansong .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2015, 35 (04) :1425-1436
[9]   αv integrins regulate cell proliferation through integrin-linked kinase (ILK) in ovarian cancer cells [J].
Cruet-Hennequart, S ;
Maubant, S ;
Luis, J ;
Gauduchon, P ;
Staedel, C ;
Dedhar, S .
ONCOGENE, 2003, 22 (11) :1688-1702
[10]   Cell-substrate interactions and signaling through ILK [J].
Dedhar, S .
CURRENT OPINION IN CELL BIOLOGY, 2000, 12 (02) :250-256