Icaritin inhibits the invasion and epithelial‐to‐mesenchymal transition of glioblastoma cells by targeting EMMPRIN via PTEN/AKt/HIF‐1α signalling

Clinical and Experimental Pharmacology and Physiology - Tập 42 Số 12 - Trang 1296-1307 - 2015
Bo Xu1,2, Chuanwu Jiang3, Hongxing Han4, Hong Liu3, Ming Tang3, Longxi Liu3, Wenyan Ji3, Xuechao Lu3, Xiuli Yang3, Yunxu Zhang3, Yongji Liu3
1Department of Neurology, Provincial Hospital of Shandong University, Jinan, Shandong, China
2Department of Neurology, The Second Affiliated Hospital, Medical College of Qingdao University, Qingdao, Shandong, China
3Department of Neurology and Department of Neurosurgery, Qingdao Hiser Medical Centre, Qingdao, Shandong, China
4Department of Neurology, Qilu Hospital of Shandong University, Jinan and Department of Neurology Linyi People's Hospital, Linyi, Shandong, China

Tóm tắt

SummaryIcaritin, a hydrolytic product of icariin from the Epimedium genus, exerts anti‐tumour effects on a variety of tumour cell types, mainly by inhibiting cell proliferation and inducing apoptosis. However, little is known about the role of icaritin in cancer invasion and epithelial‐to‐mesenchymal transition (EMT). In the present study, the glioblastoma (GBM) cell line U87MG was used as a model to investigate the effects of icaritin on the invasion and EMT of cancer cells. The results showed that icaritin significantly inhibited the invasion and EMT of GBM cells by targeting extracellular matrix metalloproteinase (EMMPRIN). Furthermore, the findings strongly indicate that the modulatory effect of icaritin on EMMPRIN is mediated via the PTEN/Akt/HIF‐1α signalling pathway. The data provide the first experimental evidence of the inhibitory effect of icaritin on cancer cell invasion and EMT, thus highlighting the potential of icaritin to be employed as a promising anti‐cancer agent in the treatment of GBM.

Từ khóa


Tài liệu tham khảo

10.1101/gad.1596707

10.1093/annonc/mdq187

10.1016/j.semradonc.2009.02.005

10.2741/1727

10.1007/s11060-013-1045-2

10.1016/j.canlet.2012.12.010

10.1007/s12264-012-1296-5

10.1007/s12094-012-0900-5

10.1038/onc.2012.52

10.1016/S0002-9440(10)62245-6

Biswas C, 1995, The human tumor cell‐derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily, Cancer Res., 55, 434

10.1074/jbc.M802694200

10.1002/prot.22577

10.1002/ijc.11288

10.1007/s10549-010-0790-6

10.1074/jbc.M111.277699

10.1007/s10620-011-1812-x

10.1002/ijc.25982

10.1016/j.ejso.2011.06.006

10.1007/s12032-012-0366-x

10.1002/1097-0215(20001001)88:1<21::AID-IJC4>3.0.CO;2-S

10.4161/cbt.4.7.1828

10.1111/j.1745-7254.2005.00076.x

10.1016/j.bone.2008.10.035

10.1016/j.neuroscience.2006.12.059

10.1016/j.cbi.2008.12.007

10.1016/j.lfs.2007.07.015

10.1371/journal.pone.0016781

10.1007/s11596-014-1305-1

10.1016/j.ejphar.2011.02.005

10.1371/journal.pone.0081657

10.1016/S0140-6736(08)61039-9

10.1007/s12013‐014‐0499‐y

10.1016/S0140-6736(10)60353-4

10.1159/000084509

10.1172/JCI39104

10.1007/s12253-013-9738-6

10.1093/carcin/bgs196

Xie J, 2015, Hispidulin prevents hypoxia‐induced epithelial‐mesenchymal transition in human colon carcinoma cells, Am. J. Cancer Res., 5, 15

10.3892/or.2015.3891

10.1016/j.canlet.2008.11.010

Sun J, 2001, Regulation of MMP‐1 and MMP‐2 production through CD147/extracellular matrix metalloproteinase inducer interactions, Cancer Res., 61, 2276

10.1038/onc.2011.149

Koga K, 2011, Synthetic emmprin peptides inhibit tumor cell‐fibroblast interaction‐stimulated upregulation of MMP‐2 and tumor cell invasion, Int. J. Oncol., 39, 657

10.1007/s12013-014-0270-4

10.7150/jca.10879

10.1111/j.1349-7006.2011.01933.x

10.1111/j.1349-7006.2009.01113.x

10.1002/cbin.10131

10.1007/s00280-006-0291-9

10.1016/S1535-6108(03)00187-9

10.1016/j.yexcr.2014.11.021

10.1016/j.taap.2013.04.031

10.1158/1535-7163.MCT-06-0526

Chen L, 2014, Succinate dehydrogenase subunit B inhibits the AMPK‐HIF‐1alpha pathway in human ovarian cancer in vitro, J. Ovarian Res., 7, 115

10.18632/oncotarget.3331

10.1158/1078-0432.CCR-14-1979

10.1371/journal.pone.0074313

Thông tin
Thông tin xuất bản

Clinical and Experimental Pharmacology and Physiology

Tập 42 Số 12

1296-1307

Thông tin tác giả