Human beta-defensin 2 promotes the proliferation of lung cancer cells through ATP-binding cassette transporter G 2

Objective: The aim of this study was to investigate the effect of human beta-defensin 2 (hBD2) and ATPbinding cassette transporter G2 (ABCG2) on the proliferation of lung cancer cells. Methods: One hundred and thirty patients with non-small cell lung cancer were recruited. All the patients underwent pulmonary lobectomy and the specimens (lung cancer tissues and corresponding non-tumor normal tissues of 130 patients) were collected. All the specimens were divided into two groups: NSCLC group (lung cancer tissues) and Control group (corresponding non-tumor normal tissues). Protein HBD2 and ABCG2 expressions were detected by immunohistochemistry. An in vitro study was also performed using A549 cells. A549 cells were treated with hBD2, proliferation was analyzed using MTT and ABCG2 expression was detected by western blotting. Next, A549 cells were pretreated with Fumitremorgin C, a selective ABCG2 inhibitor, and cell proliferation and ABCG2 expression were investigated. Results: Protein hBD2 and ABCG2 expressions in the NSCLC group were both higher compared with the control group (both P<0.01). Furthermore, hBD2 induced ABCG2 expression and A549 proliferation in a doseand time-dependent manner (both P<0.01), while these effects were inhibited by the Fumitremorgin C treatment (both P<0.01). Conclusion: hBD2 induced the proliferation of lung cancer cells through ABCG2, thus playing an important role in the development of NSCLC.

[1]  Guang-hui Li,et al.  ABCG2 regulates the pattern of self-renewing divisions in cisplatin-resistant non-small cell lung cancer cell lines. , 2014, Oncology reports.

[2]  E. Aktas,et al.  Antimicrobial peptide cathelicidin (LL- 37) and human β-defensin 2 in bronchoalveolar lavage fluid of children with pulmonary tuberculosis , 2014 .

[3]  M. Soldatkina,et al.  Expression of human beta-defensins-1-4 in thyroid cancer cells and new insight on biologic activity of hBD-2 in vitro. , 2014, Experimental oncology.

[4]  W. Stetler-Stevenson,et al.  An endogenous inhibitor of angiogenesis inversely correlates with side population phenotype and function in human lung cancer cells , 2014, Oncogene.

[5]  Y. Zhang,et al.  Camptothecin and cisplatin upregulate ABCG2 and MRP2 expression by activating the ATM/NF-κB pathway in lung cancer cells. , 2013, International journal of oncology.

[6]  Michael Thomas,et al.  A comprehensive study of polymorphisms in ABCB1, ABCC2 and ABCG2 and lung cancer chemotherapy response and prognosis , 2012, International journal of cancer.

[7]  S. Stenger,et al.  Hypoxia Triggers the Expression of Human β Defensin 2 and Antimicrobial Activity against Mycobacterium tuberculosis in Human Macrophages , 2012, The Journal of Immunology.

[8]  E. Zhuravel,et al.  Immunohistochemical analysis of beta-defensin-2 expression in human lung tumors. , 2010, Experimental oncology.

[9]  M. Decramer,et al.  Genomic copy number determines functional expression of {beta}-defensin 2 in airway epithelial cells and associates with chronic obstructive pulmonary disease. , 2010, American journal of respiratory and critical care medicine.

[10]  Eduardo Guaní-Guerra,et al.  Antimicrobial peptides: general overview and clinical implications in human health and disease. , 2010, Clinical immunology.

[11]  E. Solary,et al.  Human defensins as cancer biomarkers and antitumour molecules. , 2009, Journal of proteomics.

[12]  E. Zhuravel,et al.  Expression of human beta-defensins-1, 2 and 4 mRNA in human lung tumor tissue: a pilot study. , 2008, Experimental oncology.

[13]  Laurence Zitvogel,et al.  Toll-like receptor 4–dependent contribution of the immune system to anticancer chemotherapy and radiotherapy , 2007, Nature Medicine.

[14]  Zhinan Xu,et al.  Recent advances in the research and development of human defensins , 2006, Peptides.

[15]  M. Nakazato,et al.  Elevated Serum β-Defensins Concentrations in Patients with Lung Cancer , 2004 .

[16]  G. Diamond,et al.  Transcriptional Regulation of β-Defensin Gene Expression in Tracheal Epithelial Cells , 2000, Infection and Immunity.

[17]  L. Doyle,et al.  A multidrug resistance transporter from human MCF-7 breast cancer cells. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[18]  G. Galbraith Antimicrobial Peptides Human β-Defensins Stimulate Epidermal Keratinocyte Migration, Proliferation and Production of Proinflammatory Cytokines and Chemokines , 2008 .