Skip to main content

Advertisement

SpringerLink
Log in

Lipoxin A4 Suppresses Lipopolysaccharide-Induced Hela Cell Proliferation and Migration via NF-κB Pathway

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Uterine cervical carcinoma (UCC) is one of the most common malignant tumors in females, and UCC has a close relationship with chronic cervicitis. As the endogenous “braking signal,” lipoxins can regulate anti-inflammation and the resolution of inflammation. We investigated the effect of lipoxin A4 (LXA4) on the proliferation, apoptosis, and migration in lipopolysaccharide (LPS)-stimulated Hela cells. We demonstrated that LXA4 could significantly suppress p53, cyclin D1 expression, and migration of LPS-stimulated Hela cells via nuclear factor-κB (NF-κB) pathway, and these effects could be blocked by Boc-2, the specific inhibitor of FPR2/ALX (the receptor of LXA4). We presented evidence for a novel role of LXA4 on the proliferation and migration in LPS-stimulated Hela cells, and FPR2/ALX was involved in the procedures. These results showed that LXA4 could be a possible candidate for UCC therapy, and blocking the activation of NF-κB would be an effective drug target.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

REFERENCES

  1. Finger, E.C., and A.J. Giaccia. 2010. Hypoxia, inflammation, and the tumor microenvironment in metastatic disease. Cancer Metastasis Reviews 29(2): 285–293.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Kuper, H., H.O. Adami, and D. Trichopoulos. 2000. Infections as a major preventable cause of human cancer. Journal of Internal Medicine 248(3): 171–183.

    Article  CAS  PubMed  Google Scholar 

  3. Pisani, P., D.M. Parkin, N. Munoz, et al. 1997. Cancer and infection: estimates of the attributable fraction in 1990. Cancer Epidemiology, Biomarkers & Prevention 6(6): 387–400.

    CAS  Google Scholar 

  4. Rahman, M.A., D.K. Dhar, R. Masunaga, et al. 2000. Sulindac and exisulind exhibit a significant antiproliferative effect and induce apoptosis in human hepatocellular carcinoma cell lines. Cancer Research 60(8): 2085–2089.

    CAS  PubMed  Google Scholar 

  5. Morris, T., M. Stables, and D.W. Gilroy. 2006. New perspectives on aspirin and the endogenous control of acute inflammatory resolution. ScientificWorldJournal 6: 1048–1065.

    Article  PubMed  Google Scholar 

  6. Hao, H., M. Liu, P. Wu, et al. 2011. Lipoxin A4 and its analog suppress hepatocellular carcinoma via remodeling tumor microenvironment. Cancer Letters 309(1): 85–94.

    Article  CAS  PubMed  Google Scholar 

  7. Chen, Y., H. Hao, S. He, et al. 2010. Lipoxin A4 and its analogue suppress the tumor growth of transplanted H22 in mice: the role of antiangiogenesis. Molecular Cancer Therapeutics 9(8): 2164–2174.

    Article  CAS  PubMed  Google Scholar 

  8. Balkwill, F., and L.M. Coussens. 2004. Cancer: an inflammatory link. Nature 431(7007): 405–406.

    Article  CAS  PubMed  Google Scholar 

  9. Li, Y.S., P. Wu, X.Y. Zhou, et al. 2008. Formyl-peptide receptor like 1: a potent mediator of the Ca2+ release-activated Ca2+ current ICRAC. Archives of Biochemistry and Biophysics 478(1): 110–118.

    Article  CAS  PubMed  Google Scholar 

  10. Fierro, I.M., J.L. Kutok, and C.N. Serhan. 2002. Novel lipid mediator regulators of endothelial cell proliferation and migration: aspirin-triggered-15R-lipoxin A(4) and lipoxin A(4). The Journal of Pharmacology and Experimental Therapeutics 300(2): 385–392.

    Article  CAS  PubMed  Google Scholar 

  11. Liu, S., P. Wu, D. Ye, et al. 2009. Effects of lipoxin A(4) on CoCl(2)-induced angiogenesis and its possible mechanisms in human umbilical vein endothelial cells. Pharmacology 84(1): 17–23.

    Article  CAS  PubMed  Google Scholar 

  12. Zhou, X.Y., Y.S. Li, P. Wu, et al. 2009. Lipoxin A(4) inhibited hepatocyte growth factor-induced invasion of human hepatoma cells. Hepatology Research 39(9): 921–930.

    Article  CAS  PubMed  Google Scholar 

  13. Xiong, J., P. Zeng, X. Cheng, et al. 2013. Lipoxin A4 blocks embryo implantation by controlling estrogen receptor alpha activity. Reproduction 145(4): 411–420.

    Article  CAS  PubMed  Google Scholar 

  14. Lin, F., P. Zeng, Z. Xu, et al. 2012. Treatment of Lipoxin A(4) and its analogue on low-dose endotoxin induced preeclampsia in rat and possible mechanisms. Reproductive Toxicology 34(4): 677–685.

    Article  CAS  PubMed  Google Scholar 

  15. Lin, F., X. Yu, X. Zhang, et al. 2013. A synthetic analog of lipoxin A4 partially alleviates dexamethasone-induced fetal growth restriction in rats. Placenta 34(10): 941–948.

    Article  CAS  PubMed  Google Scholar 

  16. Zheng, S., Q. Wang, Q. He, et al. 2011. Novel biphasic role of LipoxinA(4) on expression of cyclooxygenase-2 in lipopolysaccharide-stimulated lung fibroblasts. Mediators of Inflammation 2011: 745340.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Huang, Y.H., H.M. Wang, Z.Y. Cai, et al. 2014. Lipoxin A4 inhibits NF-kappaB activation and cell cycle progression in RAW264.7 cells. Inflammation 37(4): 1084–1090.

    Article  CAS  PubMed  Google Scholar 

  18. Zhou, X.Y., Z.J. Yu, D. Yan, et al. 2013. BML-111, a lipoxin receptor agonist, protected carbon tetrachloride-induced hepatic fibrosis in rats. Inflammation 36(5): 1101–1106.

    Article  CAS  PubMed  Google Scholar 

  19. Simiele, F., A. Recchiuti, D. Mattoscio, et al. 2012. Transcriptional regulation of the human FPR2/ALX gene: evidence of a heritable genetic variant that impairs promoter activity. The FASEB Journal 26(3): 1323–1333.

    Article  CAS  Google Scholar 

  20. Naugler, W.E., and M. Karin. 2008. NF-kappaB and cancer-identifying targets and mechanisms. Current Opinion in Genetics & Development 18(1): 19–26.

    Article  CAS  Google Scholar 

  21. Pikarsky, E., R.M. Porat, I. Stein, et al. 2004. NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature 431(7007): 461–466.

    Article  CAS  PubMed  Google Scholar 

  22. Greten, F.R., L. Eckmann, T.F. Greten, et al. 2004. IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118(3): 285–296.

    Article  CAS  PubMed  Google Scholar 

  23. Karin, M., and A. Lin. 2002. NF-kappaB at the crossroads of life and death. Nature Immunology 3(3): 221–227.

    Article  CAS  PubMed  Google Scholar 

  24. Clària, J., M.H. Lee, and C.N. Serhan. 1996. Aspirin-triggered lipoxins (15-epi-LX) are generated by the human lung adenocarcinoma cell line (A549)-neutrophil interactions and are potent inhibitors of cell proliferation. Molecular Medicine 2(5): 583–596.

    PubMed  Google Scholar 

  25. Karin, M. 2006. Nuclear factor-kappaB in cancer development and progression. Nature 441(7092): 431–436.

    Article  CAS  PubMed  Google Scholar 

  26. Holm, R., H. Skomedal, A. Helland, et al. 1993. Immunohistochemical analysis of p53 protein overexpression in normal, premalignant, and malignant tissues of the cervix uteri. The Journal of Pathology 169(1): 21–26.

    Article  CAS  PubMed  Google Scholar 

  27. Bracken, C.P., S.J. Wall, B. Barre, et al. 2008. Regulation of cyclin D1 RNA stability by SNIP1. Cancer Research 68(18): 7621–7628.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Abiru, S., K. Nakao, T. Ichikawa, et al. 2002. Aspirin and NS-398 inhibit hepatocyte growth factor-induced invasiveness of human hepatoma cells. Hepatology 35(5): 1117–1124.

    Article  CAS  PubMed  Google Scholar 

  29. Westermarck, J., and V.M. Kahari. 1999. Regulation of matrix metalloproteinase expression in tumor invasion. The FASEB Journal 13(8): 781–792.

    CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (no. 81301741), Youth Science Foundation of Jiangxi Province (no. 20122BAB215007), Natural Science Foundation of Jiangxi Province (no. 20132BAB205041), and Science and Technology Plan of Education Department of Jiangxi Province (no. GJJ13037).

Conflict of Interest

The authors declare that there is no conflict of interests regarding the publication of this paper.

Author information

Authors and Affiliations

  1. Department of Pathology, The Second Affiliated Hospital of Nanchang University, No. 1 MinDe Road, Jiangxi Province, Nanchang City, 330006, China

    Hua Hao, Hua Dai, Li-Qing Wu & Fan-Rong Liu

  2. The Special Wards, The Second Affiliated Hospital of Nanchang University, No. 1 MinDe Road, Jiangxi Province, Nanchang City, 330006, China

    Fen Xu

  3. Department of Critical Care Medicine, The Third People’s Hospital of Bengbu City, No. 38 Victory Road, Anhui Province, Bengbu City, 233000, China

    Jian Hao

  4. Department of Laboratory Animal Science, Medical College of Nanchang University, No. 461 BaYi Road, Jiangxi Province, Nanchang City, 330006, China

    Yuan-Qiao He

  5. Department of Pathophysiology, Medical College of Nanchang University, No. 461 BaYi Road, Jiangxi Province, Nanchang City, 330006, China

    Xiao-Yan Zhou

Authors
  1. Hua Hao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fen Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jian Hao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuan-Qiao He
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiao-Yan Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hua Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Li-Qing Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Fan-Rong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hua Hao.

Additional information

Hua Hao and Fen Xu contribute equally to this work.

ELECTRONIC SUPPLEMENTARY MATERIAL

Below is the link to the electronic supplementary material.

ESM 1

(DOC 35 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hao, H., Xu, F., Hao, J. et al. Lipoxin A4 Suppresses Lipopolysaccharide-Induced Hela Cell Proliferation and Migration via NF-κB Pathway. Inflammation 38, 400–408 (2015). https://doi.org/10.1007/s10753-014-0044-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-014-0044-6

Key Words

Search

Navigation