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Bax inhibitor-1 mediates apoptosis-resistance in human nasopharyngeal carcinoma cells

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Abstract

Bax inhibitor-1 (BI-1), a newly identified apoptosis inhibitor, has recently been found to be overexpressed in several human carcinomas and its specific down-regulation by RNA interference (RNAi) could lead to cell death. The purpose of this study is to investigate the role of BI-1 in apoptosis-resistance and the underlying mechanisms in human nasopharyngeal carcinoma (NPC) cells. Our results showed that BI-1 was expressed in two different human NPC cell lines, CNE-2Z and CNE-1, and specific inhibition of BI-1 expression by siRNA caused a significant increase in spontaneous apoptosis in both cell lines. Mechanistically, we demonstrated that down-regulation of BI-1 protein expression decreased the ratio of Bcl-XL/Bcl-2 with Bax protein as determined by Western blot and increased the activity of caspase-3 by colorimetric analysis, thus leading to the activation of the associated cell death pathways. Taken together, these results have provided evidence that BI-1 could serve as an important molecular target gene for the development of new therapeutic strategy against human NPCs.

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References

  1. Jia WH, Huang QH, Liao J et al (2006) Trends in incidence and mortality of nasopharyngeal carcinoma over a 20–25 year period (1978/1983–2002) in Sihui and Cangwu counties in southern China. BMC Cancer 6:178

    Article  PubMed  Google Scholar 

  2. Chou J, Lin YC, Kim J et al (2008) Nasopharyngeal carcinoma—review of the molecular mechanisms of tumorigenesis. Head Neck 30(7):946–963

    Article  PubMed  Google Scholar 

  3. Makin G, Dive C (2001) Apoptosis and cancer chemotherapy. Trends Cell Biol 11(11):S22–26

    Article  CAS  PubMed  Google Scholar 

  4. Xu Q, Reed JC (1998) Bax inhibitor-1, a mammalian apoptosis suppressor identified by functional screening in yeast. Mol Cell 1(3):337–346

    Article  CAS  PubMed  Google Scholar 

  5. Grzmil M, Kaulfuss S, Thelen P et al (2006) Expression and functional analysis of Bax inhibitor-1 in human breast cancer cells. J Pathol 208(3):340–349

    Article  CAS  PubMed  Google Scholar 

  6. Grzmil M, Thelen P, Hemmerlein B et al (2003) Bax inhibitor-1 is overexpressed in prostate cancer and its specific down- regulation by RNA interference leads to cell death in human prostate carcinoma cells. Am J Pathol 163(2):543–552

    CAS  PubMed  Google Scholar 

  7. Dykxhoorn DM, Novina CD, Sharp PA (2003) Killing the messenger: short RNAs that silence gene expression. Nat Rev Mol Cell Biol 4(6):457–467

    Article  CAS  PubMed  Google Scholar 

  8. Kim DH, Behlke MA, Rose SD et al (2005) Synthetic dsRNA Dicer substrate en hance RNAi potency and efficiency. Nat Biotechnol 23(2):222–226

    Article  CAS  PubMed  Google Scholar 

  9. Siolas D, Lerner C, Burchard J (2005) Synthetic shRNAs as potent RNAi triggers. Nat Biotechnol 23(2):227–231

    Article  CAS  PubMed  Google Scholar 

  10. Watanabe N, Lam E (2006) Arabidopsis Bax inhibitor-1 functions as an attenuator of biotic and abiotic types of cell death. Plant J 45(6):884–894

    Article  CAS  PubMed  Google Scholar 

  11. Kawai-Yamada M, Ohori Y, Uchimiya H (2004) Dissection of Arabidopsis Bax inhibitor-1 suppressing Bax-, hydrogen peroxide-, and salicylic acid-induced cell death. Plant Cell 16(1):21–32

    Article  CAS  PubMed  Google Scholar 

  12. Chae HJ, Ke N, Kim HR et al (2003) Evolutionarily conserved cytoprotection provided by Bax Inhibitor-1 homologs from animals, plants, and yeast. Gene 24(323):101–113

    Article  Google Scholar 

  13. Andersen CL, Jensen JL, Ørntoft TF (2004) Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets. Cancer Res 64(15):5245–5250

    Article  CAS  PubMed  Google Scholar 

  14. Tanaka R, Ishiyama T, Uchihara T et al (2006) Expression of the Bax inhibitor-1 gene in pulmonary adenocarcinoma. Cancer 106(3):648–653

    Article  CAS  PubMed  Google Scholar 

  15. Schmits R, Cochlovius B, Treitz G et al (2002) Analysis of the antibody repertoire of astrocytoma patients against antigens expressed by gliomas. Int J Cancer 98(1):73–77

    Article  CAS  PubMed  Google Scholar 

  16. Hückelhoven R (2004) BAX Inhibitor-1, an ancient cell death suppressor in animals and plants with prokaryotic relatives. Apoptosis 9(3):299–307

    Article  PubMed  Google Scholar 

  17. Lee GH, Kim HK, Chae SW et al (2007) Bax inhibitor-1 regulates endoplasmic reticulum stress-associated reactive oxygen species and heme oxygenase-1 expression. J Biol Chem 282(30):21618–21628

    Article  CAS  PubMed  Google Scholar 

  18. Chae HJ, Kim HR, Xu C et al (2004) BI-1 regulates an apoptosis pathway linked to endoplasmic reticulum stress. Mol Cell 15(3):355–366

    Article  CAS  PubMed  Google Scholar 

  19. Ihara-Ohori Y, Nagano M, Muto S et al (2007) Cell death suppressor Arabidopsis bax inhibitor-1 is associated with calmodulin binding and ion homeostasis. Plant Physiol 143(2):650–660

    Article  CAS  PubMed  Google Scholar 

  20. Demaurex N, Distelhorst C (2003) Cell biology. Apoptosis—the calcium connection. Science 300(5616):65–67

    Article  CAS  PubMed  Google Scholar 

  21. Xu C, Xu W, Palmer AE et al (2008) BI-1 regulates endoplasmic reticulum Ca2+ homeostasis downstream of Bcl-2 family proteins. J Biol Chem 283(17):11477–11484

    Article  CAS  PubMed  Google Scholar 

  22. Yang SP, Song ST, Song HF (2003) Advancements of antisense oligonucleotides in treatment of breast cancer. Acta Pharmacol Sin 24(4):289–295

    CAS  PubMed  Google Scholar 

  23. He GR, Zhou KY, Cai KR et al (2003) Apoptotic effects of bcl-xL antisense oligodeoxynucleotides mediated by lipofectin on cell strain CNE-2Z. Chin J Cancer 22:11–15

    CAS  Google Scholar 

  24. Min L, Zhou KY, Liang T et al (2004) Inhibitory of bcl-xL antisense oligodeoxynucleotide on growth of human nasopharyngeal carcinoma in nude mice. Chin J Oncol 26:14–16

    CAS  Google Scholar 

  25. He GR, Zhou KY, Zhang YF et al (2003) Effect of lipofectin-mediated bcl-xL antisense oligodeoxynucleotide on CNE-2Z cells. J Guangdong Med Coll 21:14

    Google Scholar 

  26. Reed JC (1995) Bcl-2: prevention of apoptosis as a mechanism of drug resistance. Hematol Oncol Clin North Am 9(2):451–473

    CAS  PubMed  Google Scholar 

  27. Liu F, He CW, Zhang YF et al (2005) RNA interference by expression of short hairpin RNAs suppresses bcl-xL gene expression in nasopharyngeal carcinoma cells. Acta Pharmacol Sin 26(2):228–234

    Article  PubMed  Google Scholar 

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Acknowledgment

This work was supported by the National Natural Science Foundation of China (No. 30672741).

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Correspondence to Keyuan Zhou.

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Zhang, M., Li, X., Zhang, Y. et al. Bax inhibitor-1 mediates apoptosis-resistance in human nasopharyngeal carcinoma cells. Mol Cell Biochem 333, 1–7 (2010). https://doi.org/10.1007/s11010-009-0198-y

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