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Article

Hypoxia-induced apoptosis is blocked by adrenomedullin via upregulation of Bcl-2 in human osteosarcoma cells

  • Authors:
    • Xue-Yuan Wu
    • Cui-Pei Hao
    • Ming Ling
    • Chi-Hua Guo
    • Wei Ma
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedics, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China, Department of Gynaecology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China, Department of Orthopedics, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
  • Pages: 787-794
    |
    Published online on: May 28, 2015
       https://doi.org/10.3892/or.2015.4011
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Abstract

Adrenomedullin (ADM), a multifunctional regulatory peptide, is potentially induced by hypoxia in physiological and pathological tissues, including many types of malignant tumors. Recent research has demonstrated that ADM expression is highly associated with the prognosis and disease severity of human osteosarcoma. However, the effect of ADM on the apoptosis of osteosarcoma cells and its possible mechanism remain to be elucidated. In the present study, we observed that mRNA and protein levels of ADM were increased in human osteosarcoma SOSP-F5M2 cells under a hypoxic microenvironment induced by cobalt chloride (CoCl2) in a time-dependent manner. Treatment with ADM significantly blunted hypoxic-induced apoptosis, evaluated by Hoechst 33342 staining and Annexin V-FITC/PI labeling. The expression of B-cell lymphoma-2 (Bcl-2) was increased by administration of ADM; meanwhile, this effect was reversed by exogenously adding U0126, a selective inhibitor of MEK or ADM22-52 (ADM-specific receptor antagonist). These results demonstrated that ADM acted as a survival factor to inhibit hypoxic-induced apoptosis via interacting with its receptors CRLR-RAMP (2,3) in osteosarcoma cells. The anti-apoptotic function of ADM was found to be mediated by upregulation of the expression of Bcl-2 partially through activation of the MEK/ERK1/2 signaling pathway. Therefore, targeting of the ADM/ADM acceptors/ERK1/2/Bcl-2 pathway may provide a potential strategy through which to induce the apoptosis of osteosarcoma cells.
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View References

1 

Cleton-Jansen AM, Anninga JK, Briaire-de Bruijn IH, Romeo S, Oosting J, Egeler RM, Gelderblom H, Taminiau AH and Hogendoorn PC: Profiling of high-grade central osteosarcoma and its putative progenitor cells identifies tumourigenic pathways. Br J Cancer. 101:1909–1918. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Zeng W, Wan R, Zheng Y, Singh SR and Wei Y: Hypoxia, stem cells and bone tumor. Cancer Lett. 313:129–136. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Zhao N, Sun BC, Sun T, Ma YM, Zhao XL, Liu ZY, Dong XY, Che N, Mo J and Gu Q: Hypoxia-induced vasculogenic mimicry formation via VE-cadherin regulation by Bcl-2. Med Oncol. 29:3599–3607. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Pàez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, Viñals F, Inoue M, Bergers G, Hanahan D and Casanovas O: Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell. 15:220–231. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Ebos JM, Lee CR, Cruz-Munoz W, Bjarnason GA, Christensen JG and Kerbel RS: Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell. 15:232–239. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Loges S, Mazzone M, Hohensinner P and Carmeliet P: Silencing or fueling metastasis with VEGF inhibitors: Antiangiogenesis revisited. Cancer Cell. 15:167–170. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Nurwidya F, Takahashi F, Minakata K, Murakami A and Takahashi K: From tumor hypoxia to cancer progression: The implications of hypoxia-inducible factor-1 expression in cancers. Anat Cell Biol. 45:73–78. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Dai ZJ, Gao J, Ma XB, Yan K, Liu XX, Kang HF, Ji ZZ, Guan HT and Wang XJ: Up-regulation of hypoxia inducible factor-1α by cobalt chloride correlates with proliferation and apoptosis in PC-2 cells. J Exp Clin Cancer Res. 31:282012. View Article : Google Scholar

9 

Knowles HJ, Schaefer KL, Dirksen U and Athanasou NA: Hypoxia and hypoglycaemia in Ewing’s sarcoma and osteosarcoma: Regulation and phenotypic effects of hypoxia-inducible factor. BMC Cancer. 10:3722010. View Article : Google Scholar

10 

El Naggar A, Clarkson P, Zhang F, Mathers J, Tognon C and Sorensen PH: Expression and stability of hypoxia inducible factor 1α in osteosarcoma. Pediatr Blood Cancer. 59:1215–1222. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Bao B, Ahmad A, Kong D, Ali S, Azmi AS, Li Y, Banerjee S, Padhye S and Sarkar FH: Hypoxia induced aggressiveness of prostate cancer cells is linked with deregulated expression of VEGF, IL-6 and miRNAs that are attenuated by CDF. PLoS One. 7:e437262012. View Article : Google Scholar : PubMed/NCBI

12 

Dai X, Ma W, He XJ and Jha RK: Elevated expression of adrenomedullin is correlated with prognosis and disease severity in osteosarcoma. Med Oncol. 30:3472013. View Article : Google Scholar

13 

Hay DL, Walker CS and Poyner DR: Adrenomedullin and calcitonin gene-related peptide receptors in endocrine-related cancers: Opportunities and challenges. Endocr Relat Cancer. 18:C1–C14. 2011. View Article : Google Scholar

14 

Kitamura K, Kangawa K, Kawamoto M, Ichiki Y, Nakamura S, Matsuo H and Eto T: Adrenomedullin: A novel hypotensive peptide isolated from human pheochromocytoma. Biochem Biophys Res Commun. 192:553–560. 1993. View Article : Google Scholar : PubMed/NCBI

15 

Nikitenko LL, Fox SB, Kehoe S, Rees MC and Bicknell R: Adrenomedullin and tumour angiogenesis. Br J Cancer. 94:1–7. 2006. View Article : Google Scholar

16 

Dai X, Ma W, Jha RK and He X: Adrenomedullin and its expression in cancers and bone. A literature review. Front Biosci (Elite Ed). 2:1073–1080. 2010. View Article : Google Scholar

17 

Kaseta MK, Khaldi L, Gomatos IP, Tzagarakis GP, Alevizos L, Leandros E, Papagelopoulos PJ and Soucacos PN: Prognostic value of bax, bcl-2, and p53 staining in primary osteosarcoma. J Surg Oncol. 97:259–266. 2008. View Article : Google Scholar

18 

Cory S, Huang DC and Adams JM: The Bcl-2 family: Roles in cell survival and oncogenesis. Oncogene. 22:8590–8607. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Ferrari S, Bertoni F, Zanella L, Setola E, Bacchini SP, Alberghini M, Versari M and Bacci G: Evaluation of P-glyco-protein, HER-2/ErbB-2, p53, and Bcl-2 in primary tumor and metachronous lung metastases in patients with high-grade osteosarcoma. Cancer. 100:1936–1942. 2004. View Article : Google Scholar : PubMed/NCBI

20 

Li Z, Takeuchi S, Ohara N and Maruo T: Paradoxically abundant expression of Bcl-2 and adrenomedullin in invasive cervical squamous carcinoma. Int J Clin Oncol. 8:83–89. 2003. View Article : Google Scholar : PubMed/NCBI

21 

Oehler MK, Norbury C, Hague S, Rees MC and Bicknell R: Adrenomedullin inhibits hypoxic cell death by upregulation of Bcl-2 in endometrial cancer cells: A possible promotion mechanism for tumour growth. Oncogene. 20:2937–2945. 2001. View Article : Google Scholar : PubMed/NCBI

22 

Park SC, Yoon JH, Lee JH, Yu SJ, Myung SJ, Kim W, Gwak GY, Lee SH, Lee SM, Jang JJ, et al: Hypoxia-inducible adrenomedullin accelerates hepatocellular carcinoma cell growth. Cancer Lett. 271:314–322. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Abasolo I, Montuenga LM and Calvo A: Adrenomedullin prevents apoptosis in prostate cancer cells. Regul Pept. 133:115–122. 2006. View Article : Google Scholar

24 

Chen X, Yang TT, Wang W, Sun HH, Ma BA, Li CX, Ma Q, Yu Z and Fan QY: Establishment and characterization of human osteosarcoma cell lines with different pulmonary metastatic potentials. Cytotechnology. 61:37–44. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Ramachandran V, Arumugam T, Hwang RF, Greenson JK, Simeone DM and Logsdon CD: Adrenomedullin is expressed in pancreatic cancer and stimulates cell proliferation and invasion in an autocrine manner via the adrenomedullin receptor, ADMR. Cancer Res. 67:2666–2675. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Martínez A, Vos M, Guédez L, Kaur G, Chen Z, Garayoa M, Pío R, Moody T, Stetler-Stevenson WG, Kleinman HK, et al: The effects of adrenomedullin overexpression in breast tumor cells. J Natl Cancer Inst. 94:1226–1237. 2002. View Article : Google Scholar : PubMed/NCBI

27 

Chen P, Pang X, Zhang Y and He Y: Effect of inhibition of the adrenomedullin gene on the growth and chemosensitivity of ovarian cancer cells. Oncol Rep. 27:1461–1466. 2012.PubMed/NCBI

28 

Shimizu S, Eguchi Y, Kosaka H, Kamiike W, Matsuda H and Tsujimoto Y: Prevention of hypoxia-induced cell death by Bcl-2 and Bcl-xL. Nature. 374:811–813. 1995. View Article : Google Scholar : PubMed/NCBI

29 

Wu X, Cai ZD, Lou LM and Zhu YB: Expressions of p53, c-MYC, BCL-2 and apoptotic index in human osteosarcoma and their correlations with prognosis of patients. Cancer Epidemiol. 36:212–216. 2012. View Article : Google Scholar

30 

Zhao Y, Zhang CL, Zeng BF, Wu XS, Gao TT and Oda Y: Enhanced chemosensitivity of drug-resistant osteosarcoma cells by lentivirus-mediated Bcl-2 silencing. Biochem Biophys Res Commun. 390:642–647. 2009. View Article : Google Scholar : PubMed/NCBI

31 

Ramos JW: The regulation of extracellular signal-regulated kinase (ERK) in mammalian cells. Int J Biochem Cell Biol. 40:2707–2719. 2008. View Article : Google Scholar : PubMed/NCBI

32 

Atabakhsh E and Schild-Poulter C: RanBPM is an inhibitor of ERK signaling. PLoS One. 7:e478032012. View Article : Google Scholar : PubMed/NCBI

33 

Deville JL, Salas S, Figarella-Branger D, Ouafik L and Daniel L: Adrenomedullin as a therapeutic target in angiogenesis. Expert Opin Ther Targets. 14:1059–1072. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Uzan B, Villemin A, Garel JM and Cressent M: Adrenomedullin is anti-apoptotic in osteoblasts through CGRP1 receptors and MEK-ERK pathway. J Cell Physiol. 215:122–128. 2008. View Article : Google Scholar

35 

Vacotto M, Coso O and Fiszer de Plazas S: Programmed cell death and differential JNK, p38 and ERK response in a prenatal acute hypoxic hypoxia model. Neurochem Int. 52:857–863. 2008. View Article : Google Scholar

36 

Johnson GL and Lapadat R: Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science. 298:1911–1912. 2002. View Article : Google Scholar : PubMed/NCBI

37 

Hers I, Vincent EE and Tavaré JM: Akt signalling in health and disease. Cell Signal. 23:1515–1527. 2011. View Article : Google Scholar : PubMed/NCBI

38 

Zambon AC, Wilderman A, Ho A and Insel PA: Increased expression of the pro-apoptotic protein BIM, a mechanism for cAMP/protein kinase A (PKA)-induced apoptosis of immature T cells. J Biol Chem. 286:33260–33267. 2011. View Article : Google Scholar : PubMed/NCBI

39 

Nagaya N, Mori H, Murakami S, Kangawa K and Kitamura S: Adrenomedullin: Angiogenesis and gene therapy. Am J Physiol Regul Integr Comp Physiol. 288:R1432–R1437. 2005. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wu X, Hao C, Ling M, Guo C and Ma W: Hypoxia-induced apoptosis is blocked by adrenomedullin via upregulation of Bcl-2 in human osteosarcoma cells. Oncol Rep 34: 787-794, 2015.
APA
Wu, X., Hao, C., Ling, M., Guo, C., & Ma, W. (2015). Hypoxia-induced apoptosis is blocked by adrenomedullin via upregulation of Bcl-2 in human osteosarcoma cells. Oncology Reports, 34, 787-794. https://doi.org/10.3892/or.2015.4011
MLA
Wu, X., Hao, C., Ling, M., Guo, C., Ma, W."Hypoxia-induced apoptosis is blocked by adrenomedullin via upregulation of Bcl-2 in human osteosarcoma cells". Oncology Reports 34.2 (2015): 787-794.
Chicago
Wu, X., Hao, C., Ling, M., Guo, C., Ma, W."Hypoxia-induced apoptosis is blocked by adrenomedullin via upregulation of Bcl-2 in human osteosarcoma cells". Oncology Reports 34, no. 2 (2015): 787-794. https://doi.org/10.3892/or.2015.4011
Copy and paste a formatted citation
x
Spandidos Publications style
Wu X, Hao C, Ling M, Guo C and Ma W: Hypoxia-induced apoptosis is blocked by adrenomedullin via upregulation of Bcl-2 in human osteosarcoma cells. Oncol Rep 34: 787-794, 2015.
APA
Wu, X., Hao, C., Ling, M., Guo, C., & Ma, W. (2015). Hypoxia-induced apoptosis is blocked by adrenomedullin via upregulation of Bcl-2 in human osteosarcoma cells. Oncology Reports, 34, 787-794. https://doi.org/10.3892/or.2015.4011
MLA
Wu, X., Hao, C., Ling, M., Guo, C., Ma, W."Hypoxia-induced apoptosis is blocked by adrenomedullin via upregulation of Bcl-2 in human osteosarcoma cells". Oncology Reports 34.2 (2015): 787-794.
Chicago
Wu, X., Hao, C., Ling, M., Guo, C., Ma, W."Hypoxia-induced apoptosis is blocked by adrenomedullin via upregulation of Bcl-2 in human osteosarcoma cells". Oncology Reports 34, no. 2 (2015): 787-794. https://doi.org/10.3892/or.2015.4011
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