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CacyBP/SIP enhances multidrug resistance of pancreatic cancer cells by regulation of P-gp and Bcl-2

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Abstract

Our former report indicates that calcyclin-binding protein or Siah-1-interacting protein (CacyBP/SIP) is over-expressed in the SGC7901/ADR cell line. However, the potential role of CacyBP/SIP in the development of multidrug resistance (MDR) of pancreatic cancer is still uncertain. In this paper, we investigated the role of CacyBP/SIP in MDR of pancreatic cancer cells and its possible underlying mechanisms, and found that CacyBP/SIP was over-expressed in the Gemcitabine induced MDR pancreatic cancer cell PC-3/Gem compared with its parental cell PC-3. Up-regulation of CacyBP/SIP expression could enhance resistance of chemotherapy drugs on PC-3 cells and inhibit Adriamycin-induced apoptosis accompanied by decreased accumulation of intracellular Adriamycin. Furthermore, CacyBP/SIP could significantly up-regulate the expression of P-gp, Bcl-2, and the transcription of the MDR1 gene. In addition, the decrease of CacyBP/SIP expression using RNA interference or P-gp inhibitor could partially reverse CacyBP/SIP-mediated MDR. In brief, our study demonstrated that CacyBP/SIP could enhance the MDR phenotype of pancreatic cancer cells by increasing the expression of P-gp and Bcl-2, thus inhibiting apoptosis of pancreatic cancer cell.

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References

  1. Morrow CS, Cowan KH (1988) Mechanisms and clinical significance of multidrug resistance. Oncology (Williston Park) 2(55–63):66–68

    Google Scholar 

  2. Litman T, Druley TE, Stein WD, Bates SE (2001) From MDR to MXR: new understanding of multidrug resistance systems, their properties and clinical significance. Cell Mol Life Sci 58:931–959

    Article  PubMed  CAS  Google Scholar 

  3. Lavie Y, Fiucci G, Liscovitch M (2001) Upregulation of caveolin in multidrug resistant cancer cells: functional implications. Adv Drug Deliv Rev 49:317–323

    Article  PubMed  CAS  Google Scholar 

  4. Fan D, Zhang X, Chen X, Mou Z, Hu J, Zhou S et al (2005) Bird’s-eye view on gastric cancer research of the past 25 years. J Gastroenterol Hepatol 20:360–365

    Article  PubMed  Google Scholar 

  5. Filipek A, Kuznicki J (1998) Molecular cloning and expression of a mouse brain cDNA encoding a novel protein target of calcyclin. J Neurochem 70:1793–1798

    Article  PubMed  CAS  Google Scholar 

  6. Filipek A, Wojda U (1996) p30, a novel protein target of mouse calcyclin (S100A6). Biochem J 320(Pt 2):585–587

    PubMed  CAS  Google Scholar 

  7. Matsuzawa SI, Reed JC (2001) Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses. Mol Cell 7:915–926

    Article  PubMed  CAS  Google Scholar 

  8. Schneider G, Nieznanski K, Jozwiak J, Slomnicki LP, Redowicz MJ, Filipek A (2010) Tubulin binding protein, CacyBP/SIP, induces actin polymerization and may link actin and tubulin cytoskeletons. Biochim Biophys Acta 1803:1308–1317

    Article  PubMed  CAS  Google Scholar 

  9. Chen X, Han G, Zhai H, Zhang F, Wang J, Li X et al (2008) Expression and clinical significance of CacyBP/SIP in pancreatic cancer. Pancreatology 8:470–477

    Article  PubMed  Google Scholar 

  10. Chen X, Mo P, Li X, Zheng P, Zhao L, Xue Z et al (2011) CacyBP/SIP protein promotes proliferation and G1/S transition of human pancreatic cancer cells. Mol Carcinog 50:804–810

    Article  PubMed  CAS  Google Scholar 

  11. Kilanczyk E, Gwozdzinski K, Wilczek E, Filipek A (2012) Up-regulation of CacyBP/SIP during rat breast cancer development. Breast Cancer. doi:10.1007/s12282-012-0399-1

  12. Kilanczyk E, Wasik U, Filipek A (2012) CacyBP/SIP phosphatase activity in neuroblastoma NB2a and colon cancer HCT116 cells. Biochem Cell Biol 90:558–564

    Article  PubMed  CAS  Google Scholar 

  13. Ning X, Sun S, Hong L, Liang J, Liu L, Han S et al (2007) Calcyclin-binding protein inhibits proliferation, tumorigenicity, and invasion of gastric cancer. Mol Cancer Res 5:1254–1262

    Article  PubMed  CAS  Google Scholar 

  14. Schneider G, Filipek A (2010) S100A6 binding protein and Siah-1 interacting protein (CacyBP/SIP): spotlight on properties and cellular function. Amino Acids 41(4):773–780

    Article  PubMed  Google Scholar 

  15. Zhai H, Shi Y, Jin H, Li Y, Lu Y, Chen X et al (2008) Expression of calcyclin-binding protein/Siah-1 interacting protein in normal and malignant human tissues: an immunohistochemical survey. J Histochem Cytochem 56:765–772

    Article  PubMed  CAS  Google Scholar 

  16. Zhao Y, You H, Liu F, An H, Shi Y, Yu Q et al (2002) Differentially expressed gene profiles between multidrug resistant gastric adenocarcinoma cells and their parental cells. Cancer Lett 185:211–218

    Article  PubMed  CAS  Google Scholar 

  17. Shi Y, Hu W, Yin F, Sun L, Liu C, Lan M et al (2004) Regulation of drug sensitivity of gastric cancer cells by human calcyclin-binding protein (CacyBP). Gastric Cancer 7:160–166

    Article  PubMed  CAS  Google Scholar 

  18. Shi Y, Zhai H, Wang X, Wu H, Ning X, Han Y et al (2002) Multidrug-resistance-associated protein MGr1-Ag is identical to the human 37-kDa laminin receptor precursor. Cell Mol Life Sci 59:1577–1583

    Article  PubMed  CAS  Google Scholar 

  19. Guo C, Ding J, Yao L, Sun L, Lin T, Song Y et al (2005) Tumor suppressor gene Runx3 sensitizes gastric cancer cells to chemotherapeutic drugs by downregulating Bcl-2, MDR-1 and MRP-1. Int J Cancer 116:155–160

    Article  PubMed  CAS  Google Scholar 

  20. Cheng W, Liu T, Wan X, Gao Y, Wang H (2012) MicroRNA-199a targets CD44 to suppress the tumorigenicity and multidrug resistance of ovarian cancer-initiating cells. FEBS J 279:2047–2059

    Article  PubMed  CAS  Google Scholar 

  21. Liu Q, Mittal R, Emami CN, Iversen C, Ford HR, Prasadarao NV (2012) Human isolates of Cronobacter sakazakii bind efficiently to intestinal epithelial cells in vitro to induce monolayer permeability and apoptosis. J Surg Res 176:437–447

    Article  PubMed  CAS  Google Scholar 

  22. Sun S, Ning X, Liu J, Liu L, Chen Y, Han S et al (2007) Overexpressed CacyBP/SIP leads to the suppression of growth in renal cell carcinoma. Biochem Biophys Res Commun 356:864–871

    Article  PubMed  CAS  Google Scholar 

  23. Schneider G, Filipek A (2011) S100A6 binding protein and Siah-1 interacting protein (CacyBP/SIP): spotlight on properties and cellular function. Amino Acids 41:773–780

    Article  PubMed  CAS  Google Scholar 

  24. Wang N, Ma Q, Wang Y, Ma G, Zhai H (2010) CacyBP/SIP expression is involved in the clinical progression of breast cancer. World J Surg 34:2545–2552

    Article  PubMed  Google Scholar 

  25. Agrawal M, Abraham J, Balis FM, Edgerly M, Stein WD, Bates S et al (2003) Increased 99mTc-sestamibi accumulation in normal liver and drug-resistant tumors after the administration of the glycoprotein inhibitor, XR9576. Clin Cancer Res 9:650–656

    PubMed  CAS  Google Scholar 

  26. Cabot MC, Giuliano AE, Han TY, Liu YY (1999) SDZ PSC 833, the cyclosporine A analogue and multidrug resistance modulator, activates ceramide synthesis and increases vinblastine sensitivity in drug-sensitive and drug-resistant cancer cells. Cancer Res 59:880–885

    PubMed  CAS  Google Scholar 

  27. Zhang D, Fan D (2010) New insights into the mechanisms of gastric cancer multidrug resistance and future perspectives. Future Oncol 6:527–537

    Article  PubMed  CAS  Google Scholar 

  28. Hong L, Ning X, Shi Y, Shen H, Zhang Y, Lan M et al (2004) Reversal of multidrug resistance of gastric cancer cells by down-regulation of ZNRD1 with ZNRD1 siRNA. Br J Biomed Sci 61:206–210

    PubMed  CAS  Google Scholar 

  29. Nys K, Agostinis P (2012) Bcl-2 family members: essential players in skin cancer. Cancer Lett 320:1–13

    Article  PubMed  CAS  Google Scholar 

  30. Hardwick JM, Chen YB, Jonas EA (2012) Multipolar functions of BCL-2 proteins link energetics to apoptosis. Trends Cell Biol 22:318–328

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Technician Zheng Chen for excellent experimental assistant and constructive advice. This work was funded by grants from the National Natural Science Foundation of China (No. 30973854 and No 81274002) and National Natural Science Foundation of Fujian Province (No. 2012J05157).

Conflict of interest

Not declared.

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Authors and Affiliations

  1. Department of Medical Oncology, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, Fujian, China

    Xiong Chen, Jie Li, Wenwu Wang, Xi Chen, Fangwei Xie, Zongyang Yu & Xuenong Ouyang

  2. Department of Anatomy, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China

    Peichan Zheng

  3. Department of Digestive Diseases, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China

    Zengfu Xue

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  1. Xiong Chen
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  2. Peichan Zheng
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  3. Zengfu Xue
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  4. Jie Li
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  5. Wenwu Wang
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  6. Xi Chen
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  7. Fangwei Xie
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  8. Zongyang Yu
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  9. Xuenong Ouyang
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Corresponding authors

Correspondence to Xiong Chen or Xuenong Ouyang.

Additional information

Xiong Chen and Peichan Zheng contributed equally to this study.

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Chen, X., Zheng, P., Xue, Z. et al. CacyBP/SIP enhances multidrug resistance of pancreatic cancer cells by regulation of P-gp and Bcl-2. Apoptosis 18, 861–869 (2013). https://doi.org/10.1007/s10495-013-0831-9

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