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BCRP Expression in VX2 Rabbit Liver Tumours and its Effects on Tumour Recurrence, Metastasis and Treatment Tolerability

  • Li, Cai-Xia (Department of Radiology, Qilu Hospital of Shandong University) ;
  • Zhang, Kai (Department of Radiology, Qilu Hospital of Shandong University) ;
  • Xie, Fu-Bo (Department of Radiology, Qilu Hospital of Shandong University)
  • Published : 2013.09.30

Abstract

Objective: This study aimed to investigate the effects of BCRP expression on tumor recurrence, metastasis and treatment tolerability. Methods: A VX2 rabbit liver tumor model was established. Division was randomly into 4 groups: namely saline control group; A group, given hydration lipiodol; B group, Ad-p53; and C group, Ad-p53+hydration lipiodol. After the intervention, samples were collected to detect the BCRP, MMP-2, VEGF and PCNA. Results: The expression of BCRP, MMP-2, PCNA and VEGF in tumors in Group A had no significant difference when compared with the control group, while in B and C group, the values were significantly lower (P<0.05). BCRP positive expression in metastatic lesions significantly increased (P<0.05), and was correlated with MMP-2 ($X^2=6.172$, P=0.0131). Conclusions: BCRP may play an important role in mediating liver cancer multidrug resistance to chemotherapy, and may be correlated with tumor recurrence and metastasis, which leads to weakened treatment effect. Ad-P53 can down-regulate the expression of related genes, playing a role in multidrug resistance reversal and increased sensitivity in liver cancer treatment.

Keywords

References

  1. Abaan OD, Mutlu PK, Baran Y, Atalay C, Gunduz U (2009). Multidrug resistance mediated by MRP1 gene overexpression in breast cancer patients. Cancer Invest, 27, 201-5. https://doi.org/10.1080/07357900802173562
  2. An G, Morris ME (2010). Effects of single and multiple flavonoids on BCRP-mediated accumulation, cytotoxicity and transport of mitoxantrone in vitro. Pharm Res, 27, 1296-308. https://doi.org/10.1007/s11095-010-0108-8
  3. Ayed A, Hupp T (2010). Molecular Biology Intelligence unit. P53. Landes Bioscience, pp30-1.
  4. Bomken S, Fisser K, Heidenreich O, Vormoor J (2010). Understanding the cancer stem cell. Br J Cancer, 103, 439-45. https://doi.org/10.1038/sj.bjc.6605821
  5. Bortolomai I, Canevari S, Facetti I, et al (2010). Tumor initiating cells: Development and critical characterization of a model derived from the A431 carcinoma cell line forming spheres in suspension. Cell Cycle, 9, 1194-206. https://doi.org/10.4161/cc.9.6.11108
  6. Ding XW, Wu JH, Jiang CP (2010). ABCG2:A Potential marker of stem cells and novel target in stem cell and cancer therapy. Life Sci, 86, 631-7. https://doi.org/10.1016/j.lfs.2010.02.012
  7. Getz GS, Reardon CA (2011). The ABC transporters and the thickening cholesterol plot. Curr Opin Lipidol, 22, 72-3. https://doi.org/10.1097/MOL.0b013e328342b0fc
  8. Hampras SS, Sucheston L,Weiss J, et al (2010). Genetic polymorphisms of ATP-binding cassette (ABC) Proteins, overall survival and drug toxicity in patients with acute myeloid leukemia. Int J Mol Epidemiol Genet, 1, 201-7.
  9. Lim ST, Miller NL, Nam JO, et al (2010). Pyk2 inhibition of p53 as an adaptive and intrinsic mechanism facilitating cell proliferation and survival. Biol Chem, 285, 1743-53. https://doi.org/10.1074/jbc.M109.064212
  10. Lindner D, Zietsch C, Becher PM, et al (2012). Differential expression of matrix metalloproteases in human fibroblasts with different origins. Biochem Res Int, 2012, 875742.
  11. Lutgendorf SK, Lamkin DM, Jennings NB, et al (2008). Biobehavioral influences on matrix metalloproteinase expression in ovarian carcinoma. Clin Cancer Res, 14, 6839-46. https://doi.org/10.1158/1078-0432.CCR-08-0230
  12. Maier P, Spier I, Laufs S (2010). Chemoprotection of human hematopoietic stem cells by simultaneous lentiviral overexpression of multidrug resistance-1 and O(6)- methylguanine-DNA Methyltransferase (P140K). Gene Ther, 17, 389-99. https://doi.org/10.1038/gt.2009.133
  13. McGowan PM, Duffy MJ (2008). Matrix metalloproteinase expression and outcome in patients with breast cancer: analysis of a published database. Ann Oncol, 19, 1566-72. https://doi.org/10.1093/annonc/mdn180
  14. Mullins CS, Eisold S, Klar E, Linnebacher M (2011). Multidrugresistance proteins are weak tumor associated antigens for colorectal carcinoma. BMC Immunol, 10, 38.
  15. Natarajan K, Xie Y, Baer MR, Ross DD (2012). Role of breast cancer resistance protein (BCRP/ABCG2) in cancer drug resistance. Biochem Pharmacol, 83, 1084-103. https://doi.org/10.1016/j.bcp.2012.01.002
  16. Ni Z, Bikadi Z, Rosenberg MF, Mao Q (2010). Structure and function of the human breast cancer resistance protein (BCRP/ABCG2). Curr Drug Metab, 11, 603-17. https://doi.org/10.2174/138920010792927325
  17. Oh WK, Cho KB, Hien TT, et al (2010). Amurensin G, a potent natural SIRT1 inhibitor,rescues doxorubicin responsiveness via down-regulation of multidrug resistance. Mol Pharmacol, 78, 855-64. https://doi.org/10.1124/mol.110.065961
  18. Oliveira LR, Jeffrey SS, Ribeiro A (2010). Stem cells in human breast cancer. Histol Histopathol, 25, 371-85.
  19. Robey RW, Polgar O, Deeken J, To KW, Bates SE (2007). ABCG2:determining its relevance in clinical drug resistance. Cancer Metastasis Rev, 26, 39-57. https://doi.org/10.1007/s10555-007-9042-6
  20. Robey RW, To KK, Polgar O, et al (2009). ABCG2: a perspective. Adv Drug Deliv Rev, 61, 3-13. https://doi.org/10.1016/j.addr.2008.11.003
  21. Schwavedissen HE, Kroemer HK (2010). In vitro and in vivo evidence for the importance of breast cancer resistance protein transporters (BCRP/MXR/ABCP/ABCG2). Handb Exp Pharmacol, 201, 325-71.
  22. Sengupta A, Cancelas JA (2010). Cancer stem cells: a stride towards cancer cure. J Cell Physiol, 225, 7-14. https://doi.org/10.1002/jcp.22213
  23. Song MJ, Chun HJ, Song S, et al (2012). Comparative study between doxorubicin-eluting beads and conventional transarterial chemoembolization for treatment of hepatocellular carcinoma. J Hepatol, 57, 1233-50.
  24. Takayasu K, Arii S, Kudo M, et al (2012). Superselective transarterial chemoembolization for hepatocellular carcinoma. Validation of treatment algorithm proposed by Japanese guidelines. J Hepatol, 56, 886-92. https://doi.org/10.1016/j.jhep.2011.10.021
  25. Wittgen HG, Van JJ, Van PH, et al (2011). Canabinoid type 1 receptor antagonists modulate transport activity of multidrug resistance associated proteins MRP1, MRP2, MRP3 and MRP4. Drug Metab Dispos, 39, 1294-302. https://doi.org/10.1124/dmd.110.037812
  26. Yusuf RU, Omar SA, Ngure RM (2010). The effect of point mutations in dihydrofolate reductase genes and multidrug resistance gene186 on treatment of falciparum malaria in Sudan. J Infect Dev Ctries, 4, 61-9.