|
|
|
| Preliminary Study on HCC EMT Transformation and Drug Resistance Induced by Hypoxia |
| JIAO Min, JING Li, RUAN Zhi-ping, et al |
| Department of Oncology, the First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shaanxi, 710061 |
|
|
|
|
Abstract 【Objective】To observe the effect of hypoxia on invasion and metastasis of hepatocellular carcinoma (HCC) cells and to investigate the mechanism of drug resistance in HCC cells induced by hypoxia.【Methods】HCC hypoxia model was established by using HepG2 and SMMC-7721 cells. The morphological changes were observed by inverted microscope; invasion and metastasis of tumor cells in vitro were detected by Transwell migration and invasion assays; the cell activity was tested by MTT assay. Epithelial mesenchymal transition (EMT) related protein including E-cadherin, Vinmentin, N-cadherin and the expression of tumor drug resistance gene ABCG2 were detected by Western blotting. Apoptosis and cell cycle changes were detected by flow cytometry.【Results】HCC cells transformed from epithelial like phenotype to mesenchymal cell like phenotype after 48 h of hypoxia culture; the expression of E-cadherin decreased significantly and the expression of Vimentin and N-cadherin increased significantly under hypoxia (P<0.05); at the same time, the migration and invasion ability of HCC cells increased significantly under hypoxia (P<0.05); hypoxia can lead to a significant increase in the number of HepG2 and SMMC-7721 arrested in quiescent phase (G0/G1); under hypoxia, the resistance of HCC cells to cisplatin was significantly increased (P<0.05); the expression of ABCG2 protein was increased under hypoxic conditions (P<0.05).【Conclusion】Hypoxia induces HCC EMT transformation and causes invasion and metastasis. At the same time, hypoxia may also induce resistance to cisplatin.
|
|
Received: 13 September 2017
|
|
|
|
|
|
[1]Sartorius K,Sartorius B,Aldous C,et al.Global and country underestimation of hepatocellular carcinoma (HCC) in 2012 and its implications[J].Cancer Epidemiol,2015,39(3):284-290.
[2]Bosetti C,Turati F,La Vecchia C.Hepatocellular carcinoma epidemiology [J].Best Pract Res Clin Gastroenterol,2014,28(5):753-770.
[3]Santamaria PG,Moreno-Bueno G,Portillo F,Cano A.EMT:Present and future in clinical oncology[J].Mol Oncol,2017,11(7):718-738.
[4]Brahimi-Horn MC,Chiche J,Pouyssegur J.Hypoxia and cancer[J].J Mol Med,2007,85:1301-1307.
[5]Rankin EB,Nam JM,Giaccia AJ.Hypoxia:signaling the metastatic cascade[J].Trends Cancer,2016,2(6):295-304.
[6]Imai T,Horiuchi A,Wang C,et al.Hypoxia attenuates the expression of E-cadherin via upregulation of SNAIL in ovarian carcinoma cells[J].Am J Pathol,2003,163 (4):1437-1447.
[7]Lester RD,Jo M,Montel V,et al.uPAR induces epithelial-mesenchymal transition in hypoxic breast cancer cells[J].J Cell Biol,2007,178 (3):425-436.
[8]Krishnamachary B,Zagzag D,Nagasawa H,et al.Hypoxia-inducible factor-1-dependent repression of E-cadherin in von Hippel-Lindau tumor suppressor-null renal cell carcinoma mediated by TCF3,ZFHX1A,and ZFHX1B[J].Cancer Res,2006,66 (5):2725-2731. |
|
|
|
2017, Vol. 34 
