Please wait a minute...
Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2009, Vol. 3 Issue (3) : 303-308     DOI: 10.1007/s11684-009-0060-3
Research articles |
Effects of hypoxia inducible factor-1alpha siRNA on the invasion of human Hela cells and expression of related proteins
Bin YANG MS 1, Xianglin YUAN 2, Yanmei ZOU 2, Qingsong XI 2, Guoxian LONG 2, Qiang FU 2, Guangyuan HU MM 2,
1.Center of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;First Ward of Internal Medicine, Tumor Hospital of Hubei Province, Wuhan 430067, China; 2.Center of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;
Download: PDF(262 KB)  
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract  The effects of hypoxia on the invasion and the related protein expression of Hela cells and the role of hypoxia inducible factor-1α (HIF-1α) were investigated. The Hela cells were divided into three groups, namely, H0 (non-transfected Hela cells), H1 (pGenesil-1 empty plasmid-transfected Hela cells), and H2 (HIF-1α-shRNA plasmid-transfected Hela cells), and were cultured under hypoxia (1% O2) and normoxia for 48h. The expression of HIF-1α, E-cadherin, β-catenin, and actin was detected using Western blot. The scratch test and the invasion assay were applied to examine the invasion in each group. The expression of HIF-1α, E-cadherin, and β-catenin in tumor grafts was assayed immunohistochemically. Western blot results revealed that the bands of HIF-1α, E-cadherin, β-catenin, and actin proteins were detected in the H0 and H1 groups under hypoxia for 48h. The expression of E-cadherin, β-catenin, and actin was detected in the H2 group under hypoxia for 48h, and normoxia. In the H0, H1, and H2 groups under normoxia, and the H2 group under hypoxia for 48h, no expression of HIF-1α was detectable. The scratch test showed that the invasive ability in the H2 group was significantly alleviated. Immunohistochemically, it was found that there was a significant difference in the expression of HIF-1α, E-cadherin, and β-catenin between the H1 and H2 groups (P<0.05), but the difference was not significant between the H0 and H1 groups. It was concluded that the effects of hypoxia on the invasion of human cervical cancer Hela cells and the expression of related proteins (E-cadherin, β-catenin, and actin) depend on HIF-1α.
Keywords hypoxia      actin;β-catenin      E-cadherin      invasion      
Issue Date: 05 September 2009
URL:     OR
Fidler I J. The pathogenesis of cancer metastasis: the seed and oil hypothesisrevisited. Nat Rev Cancer, 2003, 3(6): 453―458

doi: 10.1038/nrc1098
Rivard N. Phosphatidylinositol3-kinase: a key regulator in adherent junction formation and function. Front Biosci, 2009, 14: 510―522

doi: 10.2741/3259
Sonq Y, Wang W, Qu X, Sun S. Effects ofhypoxia inducible factor-1alpha (HIF-1alpha) on the growth & adhesionin tongue squamous cell carcinoma cells. Indian J Med Res. 2009, 129(2): 154―163
Song I S, Wang A G, Yoon S Y, Kim J M, Kim J H, Lee D S, Kim N S. Regulation of glucose metabolism-relatedgenes and VEGF by HIF-1alpha and HIF-1beta, but not HIF-2alpha, ingastric cancer. Exp Mol Med, 2009, 41(1): 51―58

doi: 10.3858/emm.2009.41.1.007
Yuan X L, Yu S L, Zhuang L, Xie T, Yang B, Dong L L, Xiong H. Interference of HIF-1αby RNA to enhance radio sensitivity of HeLa cell tumor transplantedin BALB/c mice. Zhongguo Aizheng Zazhi, 2007, 17(4): 303―306 (in Chinese)
Sambrook J, Russell D W. The Condensed Protocols fromMolecular Cloning: a Laboratory Manual (in Chinese, trans. Huang Peitang). 3rd ed. Beijing: Science Press, 2002
Escuin D, Simons J W, Giannakakou P. Exploitation of the HIF axis for Cancer Therapy. Cancer Biol Ther, 2004, 3(7): 608―611
Fidler I J, Kim S J, Langley R R. The role of the organ microenvironment in the biologyand therapy of cancer metastasis. J CellBiochem, 2007, 101(4): 927―936

doi: 10.1002/jcb.21148
Luo Y, He D L, Ning L. Hypoxia-inducible factor-1alpha induces the epithelialmesenchymal transition of human prostatecancer cells. Chin Med, 2006, 119(9): 713―718
Ma J, Zhang L, Ru G Q, Zhao Z S, Xu W J. Upregulation of hypoxia inducible factor1alpha mRNA is associated with elevated vascular endothelial growthfactor expression and excessive angiogenesis and predicts a poor prognosisin gastric carcinoma. World J Gastroenterol, 2007, 13(11): 1680―1686
Cardone R A, Bellizzi A, Busco G, Weinman E J, Dell'Aquila M E, Casavola V, Azzariti A, Mangia A, Paradiso A, Reshkin S J. The NHERF1 PDZ2 domain regulates PKA-RhoA-p38-mediated NHE1 activationand invasion in breast tumor cells. MolBiol Cell, 2007, 18(5): 1768―1780

doi: 10.1091/mbc.E06-07-0617
Wojciak-Stothard B, Tsang L Y, Paleolog E. Hall S M, Harworth S G. Rac1 and RhoA as regulatorsof endothelial phenotype and barrier function in hypoxia-induced neonatalpulmonary hypertension. Am J Physiol LungCell Mol Physiol, 2006, 290(6): L1173―1182

doi: 10.1152/ajplung.00309.2005
Aono Y, Ariyoshi H, Tsuji Y, Ueda A, Tokunaga M, Sakon M, Monden M. Localized activation of m-calpainin human umbilical vein endothelial cells upon hypoxia. Thtomb Res, 2001, 102(4): 353―361

doi: 10.1016/S0049-3848(01)00238-9
Nelson W J, Nusse R. Convergence of Wnt, beta-catenin,and cadherin pathways. Science, 2004, 303(5663): 1483―1487

doi: 10.1126/science.1094291
Menez J, Le Maux Chansac B, Dorothée G, Vergnon I, Jalil A, Carlier M F, Chouaib S, Mami-Chouaib F. Oncogene, 2004, 23 (15): 2630―2639

doi: 10.1038/sj.onc.1207347
Calvisi D F, Ladu S, Conner E A, Factor V M, Thorgeirsson S S. Disregulation of E-cadherinin transgenic mouse models of liver cancer. Lab Invest, 2004, 84(9): 1137―1147

doi: 10.1038/labinvest.3700147
Sun S, Ning X, Zhang Y, Lu Y, Nie Y, Han S, Liu L, Du R, Xia L, He L, Fan D. Hypoxia-induciblefactor-1alpha induces Twist expression in tubular epithelial cellssubjected to hypoxia, leading to epithelial-to-mesenchymal transition. Kidney Int, 2009, 75(12): 1278―1287

doi: 10.1038/ki.2009.62
Yan W, Fu Y, Tian D, Liao J, Liu M, Wang B, Xia L, Zhu Q, Luo M. PI3 kinase/Aktsignaling mediates epithelial-mesenchymal transition in hypoxic hepatocellularcarcinoma cells. Biochem Biophys Res Commun, 2009, 2009, 382(3): 631―636
Hrroshi I, Hideyuki S, Masatoshi H. Expression of hypoxia inducible factor-1α predictsmetastasis-free survical after radiation therapy alone in stage IIIBcervical squamous cell carcinoma. Int JRadiat Oncol Biol Phys, 2004, 50(4): 865―872
Ishikawa H, Sakurai H, Hasegawa M, Mitsuhashi N, Takahashi M, Masuda N, Nakajima M, Kitamoto Y, Saitoh J, Nakano T. Expressionof Hypoxic-inducible factor-l alpha predicts metastasis-free survivalafter radiation therapy alone in stage ШB cervical squamous cellcarcinoma. Internat J Radia Oncol Phys, 2004, 60(2): 513―521

doi: 10.1016/j.ijrobp.2004.03.025
Bachtiary B, Schindl M, Potter R, Dreier B, Knocke T H, Hainfellner J A, Horvat R, Birner P. Overexpression of hypoxiainducible factor-1alpha indicates diminished response to radiotherapyand unfavorable prognosis in patients receiving radiotherapy for cervicalcancer. Clin Cancer Res, 2003, 9(6): 2234―2240
[1] Yinyin Xie,Yuanliang Zhang,Lu Jiang,Mengmeng Zhang,Zhiwei Chen,Dan Liu,Qiuhua Huang. Disabled homolog 2 is required for migration and invasion of prostate cancer cells[J]. Front. Med., 2015, 9(3): 312-321.
[2] Runlin Shi,Haibing Xiao,Tao Yang,Lei Chang,Yuanfeng Tian,Bolin Wu,Hua Xu. Effects of miR-200c on the migration and invasion abilities of human prostate cancer Du145 cells and the corresponding mechanism[J]. Front. Med., 2014, 8(4): 456-463.
[3] Carmen Chak-Lui Wong, Alan Ka-Lun Kai, Irene Oi-Lin Ng. The impact of hypoxia in hepatocellular carcinoma metastasis[J]. Front Med, 2014, 8(1): 33-41.
[4] Kai Qu, Chang Liu, Aasef M A Mansoor, Bo Wang, Jincai Chen, Liang Yu, Yi Lv. Pyogenic liver abscess as initial presentation in locally advanced right colon cancer invading the liver, gallbladder, and duodenum[J]. Front Med, 2011, 5(4): 434-437.
[5] Lei CHEN, Liang HU, Liang LI, Yuan LIU, Qian-Qian TU, Yan-Xin CHANG, He-Xin YAN, Meng-Chao WU, Hong-Yang WANG, . Dysregulation of β-catenin by hepatitis B virus X protein in HBV-infected human hepatocellular carcinomas[J]. Front. Med., 2010, 4(4): 399-411.
[6] Xue LI MM , Ping HE MM , Jie XIA MM , Shiwei SONG BS , Jinhai LU BM , Yunde LIU MM , . Effect of lanthanum chloride on growth of breast cancer cells and regulation of transcription[J]. Front. Med., 2009, 3(3): 336-340.
[7] Hong LI, Shaoqin CHEN, Yi SHU, Yongjun CHEN, Ying SU, Xin WANG, Shengquan ZOU. Effects of hydralazine and valproate on the expression of E-cadherin gene and the invasiveness of QBC939 Cells[J]. Front Med Chin, 2009, 3(2): 153-157.
[8] YANG Yingzhong, MA Lan, GE Rili, FAN Wenhong, ZHU Lingling, ZHAO Tong, WU Yan, FAN Ming. Effects of hypoxia on mRNA expression of housekeeping genes in rat brain tissue and primary cultured neural cells[J]. Front. Med., 2008, 2(3): 239-243.
[9] LI Yanhua, BI Zhigang. Ultraviolet-B induced expression of hypoxia-inducible factor 1α, transferrin receptor through EGFR/PI3K/AKT/DEC1 pathway[J]. Front. Med., 2007, 1(1): 79-86.
Full text