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Article

Downregulation of hypoxia‑inducible factor-1α inhibits growth, invasion, and angiogenesis of human salivary adenoid cystic carcinoma cells under hypoxia

  • Authors:
    • Chu Xiao
    • Yi Pan
    • Xiaoping Zeng
    • Lingyun Wang
    • Ziyang Li
    • Songxin Yan
    • Hongmei Wang
  • View Affiliations / Copyright

    Affiliations: Department of Pathophysiology Medical College of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Pathophysiology Medical College of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Immunology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Queen Mary School of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
  • Pages: 1675-1683
    |
    Published online on: July 12, 2018
       https://doi.org/10.3892/or.2018.6559
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Abstract

Surgical and medical treatments usually fail to completely remove the primary lesions of salivary adenoid cystic carcinoma (SACC), resulting in local recurrence due to its strong infiltration, hematogenous metastasis and other unique biological behaviors. Targeted gene therapy, including hypoxia‑inducible factor‑1α (HIF‑1α) therapy, sheds new light on the treatment of salivary gland tumors. However, the mechanisms underlying the downregulation of HIF‑1α expression in SACC have not been well studied. The present study aimed to determine the effects of HIF‑1α downregulation on the proliferation, invasion, apoptosis, cell cycle and angiogenesis of hypoxic SACC‑83 cells, and to elucidate the molecular mechanisms underlying these effects. Western blot analysis was used to evaluate the protein expression levels of HIF‑1α and matrix metalloproteinase‑2 (MMP‑2). Angiogenesis and the protein expression of vascular endothelial growth factor (VEGF) were detected by tube formation assay of human umbilical vein endothelial cells and ELISA, respectively. It was revealed that short hairpin RNA was considerably downregulated following overexpression of HIF‑1α. In addition, downregulation of HIF‑1α inhibited the expression of VEGF and MMP‑2, as well as the proliferation, invasion, migration, and tube formation of hypoxic SACC‑83 cells, while inducing apoptosis in these cells. These results suggest that the downregulation of HIF‑1α may be a novel targeted therapy for SACC.
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1 

Gondivkar SM, Gadbail AR, Chole R and Parikh RV: Adenoid cystic carcinoma: A rare clinical entity and literature review. Oral Oncol. 47:231–236. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Li LJ, Li Y, Wen YM, Liu H and Zhao HW: Clinical analysis of salivary gland tumor cases in West China in past 50 years. Oral Oncol. 44:187–192. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Umeda M, Nishimatsu N, Masago H, Ishida Y, Yokoo S, Fujioka M, Shibuya Y and Komori T: Tumor-doubling time and onset of pulmonary metastasis from adenoid cystic carcinoma of the salivary gland. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 88:473–478. 1999. View Article : Google Scholar : PubMed/NCBI

4 

Rampling R, Cruickshank G, Lewis AD, Fitzsimmons SA and Workman P: Direct measurement of pO2 distribution and bioreductive enzymes in human malignant brain tumors. Int J Radiat Oncol Biol Phys. 29:427–431. 1994. View Article : Google Scholar : PubMed/NCBI

5 

Kayama T, Yoshimoto T, Fujimoto S and Sakurai Y: Intratumoral oxygen pressure in malignant brain tumor. J Neurosurg. 74:55–59. 1991. View Article : Google Scholar : PubMed/NCBI

6 

Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, Buechler P, Isaacs WB, Semenza GL and Simons JW: Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res. 59:5830–5835. 1999.PubMed/NCBI

7 

Semenza GL: HIF-1: Mediator of physiological and pathophysiological responses to hypoxia. J Appl Physiol. 88:1474–1480. 2000. View Article : Google Scholar : PubMed/NCBI

8 

Covello KL and Simon MC: HIFs, hypoxia, and vascular development. Curr Top Dev Biol. 62:37–54. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Stoeltzing O, McCarty MF, Wey JS, Fan F, Liu W, Belcheva A, Bucana CD, Semenza GL and Ellis LM: Role of hypoxia-inducible factor 1alpha in gastric cancer cell growth, angiogenesis, and vessel maturation. J Natl Cancer Inst. 96:946–956. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Samanta D, Gilkes DM, Chaturvedi P, Xiang L and Semenza GL: Hypoxia-inducible factors are required for chemotherapy resistance of breast cancer stem cells. Proc Natl Acad Sci USA. 111:E5429–E5438. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Harada H: How can we overcome tumor hypoxia in radiation therapy? J Radiat Res. 52:545–556. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Semenza GL: Development of novel therapeutic strategies that target HIF-1. Expert Opin Ther Targets. 10:267–280. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Semenza GL and Wang GL: A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol. 12:5447–5454. 1992. View Article : Google Scholar : PubMed/NCBI

14 

Lee FS and Percy MJ: The HIF pathway and erythrocytosis. Annu Rev Pathol. 6:165–192. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Wang GL and Semenza GL: Purification and characterization of hypoxia-inducible factor 1. J Biol Chem. 270:1230–1237. 1995. View Article : Google Scholar : PubMed/NCBI

16 

Pugh CW, O'Rourke JF, Nagao M, Gleadle JM and Ratcliffe PJ: Activation of hypoxia-inducible factor-1; definition of regulatory domains within the alpha subunit. J Biol Chem. 272:11205–11214. 1997. View Article : Google Scholar : PubMed/NCBI

17 

Meijer TW, Kaanders JH, Span PN and Bussink J: Targeting hypoxia, HIF-1, and tumor glucose metabolism to improve radiotherapy efficacy. Clin Cancer Res. 18:5585–5594. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Łuczak MW, Roszak A, Pawlik P, Kędzia H, Lianeri M and Jagodziński PP: Increased expression of HIF-1A and its implication in the hypoxia pathway in primary advanced uterine cervical carcinoma. Oncol Rep. 26:1259–1264. 2011.PubMed/NCBI

19 

Sun X, Vale M, Jiang X, Gupta R and Krissansen GW: Antisense HIF-1alpha prevents acquired tumor resistance to angiostatin gene therapy. Cancer Gene Ther. 17:532–540. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 72:248–254. 1976. View Article : Google Scholar : PubMed/NCBI

21 

Shen W, Xi H, Wei B and Chen L: The prognostic role of matrix metalloproteinase 2 in gastric cancer: A systematic review with meta-analysis. J Cancer Res Clin Oncol. 140:1003–1009. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Deryugina EI and Quigley JP: Tumor angiogenesis: MMP-mediated induction of intravasation- and metastasis-sustaining neovasculature. Matrix Biol 44–46. 1–112. 2015.

23 

Chekhonin VP, Shein SA, Korchagina AA and Gurina OI: VEGF in tumor progression and targeted therapy. Curr Cancer Drug Targets. 13:423–443. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Xiong J, Yang Q, Li J and Zhou S: Effects of MDM2 inhibitors on vascular endothelial growth factor-mediated tumor angiogenesis in human breast cancer. Angiogenesis. 17:37–50. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Yan F, Wang C, Li T, Cai W and Sun J: Role of miR-21 in the growth and metastasis of human salivary adenoid cystic carcinoma. Mol Med Rep. 17:4237–4244. 2018.PubMed/NCBI

26 

Zimna A and Kurpisz M: Hypoxia-inducible factor-1 in physiological and pathophysiological angiogenesis: Applications and therapies. Biomed Res Int. 2015:5494122015. View Article : Google Scholar : PubMed/NCBI

27 

Song T, Zhang X, Wang C, Wu Y, Cai W, Gao J and Hong B: MiR-138 suppresses expression of hypoxia-inducible factor 1α (HIF-1 α) in clear cell renal cell carcinoma 786-O cells. Asian Pac J Cancer Prev. 12:1307–1311. 2011.PubMed/NCBI

28 

Roslavtceva VV, Salmina AB, Prokopenko SV, Pozhilenkova EA, Kobanenko IV and Rezvitskaya GG: The role of vascular endothelial growth factor in the regulation of development and functioning of the brain: New target molecules for pharmacotherapy. Biomed Khim. 62:124–133. 2016.(In Russian). View Article : Google Scholar : PubMed/NCBI

29 

Yu B, Miao ZH, Jiang Y, Li MH, Yang N, Li T and Ding J: c-Jun protects hypoxia-inducible factor-1alpha from degradation via its oxygen-dependent degradation domain in a nontranscriptional manner. Cancer Res. 69:7704–7712. 2009. View Article : Google Scholar : PubMed/NCBI

30 

Qi L, Zhu F, Li SH, Si LB, Hu LK and Tian H: Retinoblastoma binding protein 2 (RBP2) promotes HIF-1α-VEGF-induced angiogenesis of non-small cell lung cancer via the Akt pathway. PLoS One. 9:e1060322014. View Article : Google Scholar : PubMed/NCBI

31 

Ravi R, Mookerjee B, Bhujwalla ZM, Sutter CH, Artemov D, Zeng Q, Dillehay LE, Madan A, Semenza GL and Bedi A: Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha. Genes Dev. 14:34–44. 2000.PubMed/NCBI

32 

Tang N, Wang L, Esko J, Giordano FJ, Huang Y, Gerber HP, Ferrara N and Johnson RS: Loss of HIF-1alpha in endothelial cells disrupts a hypoxia-driven VEGF autocrine loop necessary for tumorigenesis. Cancer Cell. 6:485–495. 2004. View Article : Google Scholar : PubMed/NCBI

33 

Lee YA, Choi HM, Lee SH, Hong SJ, Yang HI, Yoo MC and Kim KS: Hypoxia differentially affects IL-1β-stimulated MMP-1 and MMP-13 expression of fibroblast-like synoviocytes in an HIF-1α-dependent manner. Rheumatology. 51:443–450. 2012. View Article : Google Scholar : PubMed/NCBI

34 

Tang YL, Liu X, Gao SY, Feng H, Jiang YP, Wang SS, Yang J, Jiang J, Ma XR, Tang YJ, et al: WIP1 stimulates migration and invasion of salivary adenoid cystic carcinoma by inducing MMP-9 and VEGF-C. Oncotarget. 6:9031–9044. 2015. View Article : Google Scholar : PubMed/NCBI

35 

Wucherpfennig AL, Li YP, Stetler-Stevenson WG, Rosenberg AE and Stashenko P: Expression of 92 kD type IV collagenase/gelatinase B in human osteoclasts. J Bone Miner Res. 9:549–556. 1994. View Article : Google Scholar : PubMed/NCBI

36 

Nagase H: Matrix metalloproteinases. A mini-review. Contrib Nephrol. 107:85–93. 1994. View Article : Google Scholar : PubMed/NCBI

37 

Liu CT, Bi KW, Huang CC, Wu HT, Ho HY, S Pang JH and Huang ST: Davallia bilabiata exhibits anti-angiogenic effect with modified MMP-2/TIMP-2 secretion and inhibited VEGF ligand/receptors expression in vascular endothelial cells. J Ethnopharmacol. 196:213–224. 2017. View Article : Google Scholar : PubMed/NCBI

38 

Wang F, Chang M, Shi Y, Jiang L, Zhao J, Hai L, Sharen G and Du H: Down-regulation of hypoxia-inducible factor-1 suppresses malignant biological behavior of triple-negative breast cancer cells. Int J Clin Exp Med. 7:3933–3940. 2014.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Xiao C, Pan Y, Zeng X, Wang L, Li Z, Yan S and Wang H: Downregulation of hypoxia‑inducible factor-1α inhibits growth, invasion, and angiogenesis of human salivary adenoid cystic carcinoma cells under hypoxia. Oncol Rep 40: 1675-1683, 2018.
APA
Xiao, C., Pan, Y., Zeng, X., Wang, L., Li, Z., Yan, S., & Wang, H. (2018). Downregulation of hypoxia‑inducible factor-1α inhibits growth, invasion, and angiogenesis of human salivary adenoid cystic carcinoma cells under hypoxia. Oncology Reports, 40, 1675-1683. https://doi.org/10.3892/or.2018.6559
MLA
Xiao, C., Pan, Y., Zeng, X., Wang, L., Li, Z., Yan, S., Wang, H."Downregulation of hypoxia‑inducible factor-1α inhibits growth, invasion, and angiogenesis of human salivary adenoid cystic carcinoma cells under hypoxia". Oncology Reports 40.3 (2018): 1675-1683.
Chicago
Xiao, C., Pan, Y., Zeng, X., Wang, L., Li, Z., Yan, S., Wang, H."Downregulation of hypoxia‑inducible factor-1α inhibits growth, invasion, and angiogenesis of human salivary adenoid cystic carcinoma cells under hypoxia". Oncology Reports 40, no. 3 (2018): 1675-1683. https://doi.org/10.3892/or.2018.6559
Copy and paste a formatted citation
x
Spandidos Publications style
Xiao C, Pan Y, Zeng X, Wang L, Li Z, Yan S and Wang H: Downregulation of hypoxia‑inducible factor-1α inhibits growth, invasion, and angiogenesis of human salivary adenoid cystic carcinoma cells under hypoxia. Oncol Rep 40: 1675-1683, 2018.
APA
Xiao, C., Pan, Y., Zeng, X., Wang, L., Li, Z., Yan, S., & Wang, H. (2018). Downregulation of hypoxia‑inducible factor-1α inhibits growth, invasion, and angiogenesis of human salivary adenoid cystic carcinoma cells under hypoxia. Oncology Reports, 40, 1675-1683. https://doi.org/10.3892/or.2018.6559
MLA
Xiao, C., Pan, Y., Zeng, X., Wang, L., Li, Z., Yan, S., Wang, H."Downregulation of hypoxia‑inducible factor-1α inhibits growth, invasion, and angiogenesis of human salivary adenoid cystic carcinoma cells under hypoxia". Oncology Reports 40.3 (2018): 1675-1683.
Chicago
Xiao, C., Pan, Y., Zeng, X., Wang, L., Li, Z., Yan, S., Wang, H."Downregulation of hypoxia‑inducible factor-1α inhibits growth, invasion, and angiogenesis of human salivary adenoid cystic carcinoma cells under hypoxia". Oncology Reports 40, no. 3 (2018): 1675-1683. https://doi.org/10.3892/or.2018.6559
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