Significance of MNK1 in prognostic prediction and chemotherapy development of epithelial ovarian cancer

被引:41
作者
Hou, S. [1 ]
Du, P. [2 ]
Wang, P. [3 ]
Wang, C. [4 ]
Liu, P. [5 ]
Liu, H. [6 ]
机构
[1] Weifang Med Univ, Yidu Cent Hosp Weifang, Dept Pharmacol, Weifang 261000, Shandong, Peoples R China
[2] Weifang Med Univ, Yidu Cent Hosp Weifang, Dept Plast Surg, Weifang 261000, Shandong, Peoples R China
[3] Qingzhou Hosp Tradit Chinese Med, Dept Pain Treatment, Weifang 261000, Shandong, Peoples R China
[4] North Sichuan Med Coll, Affiliated Hosp, Dept Reprod Ctr, Nanchong 637000, Sichuan, Peoples R China
[5] Shandong Univ, Qilu Hosp, Dept Burn & Plast Surg, 107 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China
[6] Shandong Univ, Qilu Hosp, Dept Gen Surg, 107 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China
关键词
EIF4E; Epithelial ovarian cancer; Inhibitor; MNK1; Prognosis; INITIATION-FACTOR; 4E; EIF4E PHOSPHORYLATION; CELL-GROWTH; TRANSLATION; DIAGNOSIS; THERAPY; KINASES; MTOR;
D O I
10.1007/s12094-017-1646-x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Ovarian cancer is the most lethal gynecologic malignancy worldwide with surgery as the only curative treatment. Long-term overall survival (OS) of ovarian cancer is far from satisfactory, even though significant improvement has been made in post-operative chemotherapy. One of the most important death cause is the chemoresistance due to consecutive chemotherapy. Therefore, understanding the molecular mechanisms involved in ovarian cancer development and identification of novel therapeutic targets are urgently required. Methods Immunohistochemical (IHC) staining was used to explore the expression pattern of mitogen-activated protein kinase (MAPK)-interacting kinase 1 (MNK1) in tumor tissues from 138 epithelial ovarian cancer (EOC) patients. Clinicopathological data were subjected to Kaplan-Meier survival and Cox multivariate analyses to evaluate the prognostic value of MNK1 in EOC. Overexpression and silencing procedures were performed on OVCAR-5 cells to investigate the mechanisms of MNK1 in regulating EOC development. The anti-tumor effects of CGP57380, a specific MNK inhibitor, were examined by cell viability assay. Results Higher MNK1 expression showed significant relationship with advanced FIGO stage and positive lymph node metastasis of EOC. Univariate and multivariate analyses revealed that MNK1 was an independent prognostic factor for OS of EOC patients. In vitro study demonstrated that MNK1 can promote cell proliferation through regulating the phosphorylation level of eukaryotic initiation factor 4E. In addition, inhibition of MNK1 by CGP57380 significantly down-regulated the OVCAR-5 cell viability. Conclusion High MNK1 expression in EOC tissues indicates poor clinical outcomes, and MNK1 can act as a potential target for novel chemotherapy development towards EOC.
引用
收藏
页码:1107 / 1116
页数:10
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