Effect of Human Equilibrative Nucleoside Transports on Cytotoxicity of 5-Fluorouracil in Breast Cancer Cells_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 GAOYi-ming ,  ZHAOChun-ying

Department of Breast Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;

Corresponding author：

ZHAOChun-ying, Email: cyzhao59@163.com

Keywords：

Cytotoxicity; Breast cancer cell line; Nucleoside transporter; 5-fluorouracil

DOI：

10.7507/1007-9424.20140144

Video：

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Objective To investigate the effect of expressions of nucleoside transporters subtype (hENT1 and hENT2) on 5-fluorouracil(5-FU) cytotoxicity in breast cancer cell lines(MDA-MB-231, MDA-MB-468, SK-BR-3, MCF-7). Methods Four breast cancer cell lines were chosen to detect the mRNA expressions of hENT1 and hENT2 by RT-PCR. Cells were incubated in the medium with a serial concentrations of 5-FU from 1.28×10⁴ ng/L to 2.00×10⁸ ng/L for 48 h. Then the cell proliferation in each cell line was measured by MTT assay and the IC₅₀ was evaluated. Results ①The mRNA expressions of hENT1 and hENT2 in the MDA-MB-231, MDA-MB-468, or SK-BR-3 cells were significantly higher than thoes in the MCF-7 cells(P < 0.05). The mRNA expression of hENT2 was detected in the MDA-MB-231, MDA-MB-468, or SK-BR-3 cells, not detected in the MCF-7 cells. 2MTT showed that IC₅₀ of 5-FU in the MDAMB-231, MDA-MB-468, or SK-BR-3 cells was significantly lower than that in the MCF-7 cells(P < 0.05). There was no statistical difference of IC₅₀ among the three lines(MDA-MB-231, MDA-MB-468, and SK-BR-3)(P > 0.05).③The three lines(MDA-MB-231, MDA-MB-468, and SK-BR-3) with lower IC₅₀ of 5-FU highly expressed hENTs, and MCF-7 cell with the higher IC₅₀ of 5-FU expressed less hENTs. Conclusions The expressions of hENTs in breast cancer cell lines can significantly influence 5-FU cytotoxic effect. It is implicated that the hENTs expressions might be the clue to the choice of nucleoside anticancer drugs in clinic.

Citation： GAOYi-ming, ZHAOChun-ying. Effect of Human Equilibrative Nucleoside Transports on Cytotoxicity of 5-Fluorouracil in Breast Cancer Cells. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2014, 21(5): 599-602. doi: 10.7507/1007-9424.20140144 Copy

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14.	Carroll JP, Protani MM, Nguyen L, et al.Toxicity and tolerability of adjuvant breast cancer chemotherapy in obese women[J].Med Oncol, 2014, 31(4):881.
15.	Liu XH, Man YN, Cao R, et al.Individualized chemotherapy based on organ selectivity:a retrospective study of vinorelbine and capecitabine for patients with metastatic breast cancer[J].Curr Med Res Opin, 2014 Feb 14.[Epub ahead of print].
16.	Azuma Y, Hata K, Sai K, et al.Significant association between hand-foot syndrome and efficacy of capecitabine in patients with metastatic breast cancer[J].Biol Pharm Bull, 2012, 35(5):717-724.
17.	Roos-van Groningen MC, Eikmans M, Baelde HJ, et al.Improvement of extraction and processing of RNA from renal biopsies[J].Kidney Int, 2004, 65(1):97-105.
18.	Govindarajan R, Bakken AH, Hudkins KL, et al.In situ hybridization and immunolocalization of concentrative and equilibrative nucleoside transporters in the human intestine, liver, kidneys, and placenta[J].Am J Physiol Regul Integr Comp Physiol, 2007, 293(5):R1809-R1822.
19.	Guzmán-Gutiérrez E, Sandoval C, Nova E, et al.Differential expression of functional nucleoside transporters in non-differentiated and differentiated human endothelial progenitor cells[J].Placenta, 2010, 31(10):928-936.
20.	Redzic ZB, Malatiali SA, Grujicic D, et al.Expression and functional activity of nucleoside transporters in human choroid plexus[J].Cerebrospinal Fluid Res, 2010, 7:2.
21.	Perrone G, Morini S, Santini D, et al.Human equilibrative nucleoside transporter 1 and carcinoma of the ampulla of Vater:expression differences in tumour histotypes[J].Eur J Histochem, 2010, 54(3):e38.
22.	Park JS, Hughes SJ, Cunningham FK, et al.Identification of cysteines involved in the effects of methanethiosulfonate reagents on human equilibrative nucleoside transporter 1[J].Mol Pharmacol, 2011, 80(4):735-746.
23.	Procházková A, Liu S, Friess H, et al.Determination of 5-fluorouracil and 5-fluoro-2'-deoxyuridine-5'-monophosphate in pancreatic cancer cell line and other biological materials using capillary electrophoresis[J].J Chromatogr A, 2001, 916(1/2):215-224.
24.	Mohelnikova-Duchonova B, Melichar B.Human equilibrative nucleoside transporter 1(hENT1):do we really have a new predictive biomarker of chemotherapy outcome in pancreatic cancer patients?[J].Pancreatology, 2013, 13(6):558-563.

1. Edwards BK, Noone AM, Mariotto AB, et al.Annual report to the nation on the status of cancer, 1975-2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer[J].Cancer, 2013 Dec 16.[Epub ahead of print].
2. Andrade DA, Zucca-Matthes G, Vieira RA, et al.Neoadjuvant chemotherapy and pathologic response:a retrospective cohort[J].Einstein (Sao Paulo), 2013, 11(4):446-450.
3. Navin NE.Tumor evolution in response to chemotherapy:phenotype versus genotype[J].Cell Rep, 2014, 6(3):417-419.
4. Greenhalf W, Ghaneh P, Neoptolemos JP, et al.Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the ESPAC-3 trial[J].J Natl Cancer Inst, 2013 Dec 3.[Epub ahead of print].
5. Li B, Gu L, Hertz L, et al.Expression of nucleoside transporter in freshly isolated neurons and astrocytes from mouse brain[J].Neurochem Res, 2013, 38(11):2351-2358.
6. Pérez-Torras S, Vidal-Pla A, Cano-Soldado P, et al.Concentrative nucleoside transporter 1(hCNT1) promotes phenotypic changes relevant to tumor biology in a translocation-independent manner[J].Cell Death Dis, 2013, 4:e648.
7. Kong W, Engel K, Wang J.Mammalian nucleoside transporters[J].Curr Drug Metab, 2004, 5(1):63-84.
8. Yao SY, Ng AM, Cass CE, et al.Nucleobase transport by human equilibrative nucleoside transporter 1(hENT1)[J].J Biol Chem, 2011, 286(37):32552-32562.
9. Guillén-Gómez E, Pinilla-Macua I, Pérez-Torras S, et al.New role of the human equilibrative nucleoside transporter 1(hENT1) in epithelial-to-mesenchymal transition in renal tubular cells[J].J Cell Physiol, 2012, 227(4):1521-1528.
10. Lane J, Martin TA, McGuigan C, et al.The differential expression of hCNT1 and hENT1 in breast cancer and the possible impact on breast cancer therapy[J].J Exp Ther Oncol, 2010, 8(3):203-210.
11. 唐金海, 姚宇锋.早期乳腺癌的诊断和外科治疗进展[J].中国普外基础与临床杂志, 2011, 18(9):913-916.
12. Saleh RR, Bouganim N, Hilton J, et al.Neoadjuvant endocrine treatment for breast cancer:from bedside to bench and back again?[J].Curr Oncol, 2014, 21(1):e122-e128.
13. Damaraju VL, Mowles D, Yao S, et al.Role of human nucleoside transporters in the uptake and cytotoxicity of azacitidine and decitabine[J].Nucleosides Nucleotides Nucleic Acids, 2012, 31(3):236-255.
14. Carroll JP, Protani MM, Nguyen L, et al.Toxicity and tolerability of adjuvant breast cancer chemotherapy in obese women[J].Med Oncol, 2014, 31(4):881.
15. Liu XH, Man YN, Cao R, et al.Individualized chemotherapy based on organ selectivity:a retrospective study of vinorelbine and capecitabine for patients with metastatic breast cancer[J].Curr Med Res Opin, 2014 Feb 14.[Epub ahead of print].
16. Azuma Y, Hata K, Sai K, et al.Significant association between hand-foot syndrome and efficacy of capecitabine in patients with metastatic breast cancer[J].Biol Pharm Bull, 2012, 35(5):717-724.
17. Roos-van Groningen MC, Eikmans M, Baelde HJ, et al.Improvement of extraction and processing of RNA from renal biopsies[J].Kidney Int, 2004, 65(1):97-105.
18. Govindarajan R, Bakken AH, Hudkins KL, et al.In situ hybridization and immunolocalization of concentrative and equilibrative nucleoside transporters in the human intestine, liver, kidneys, and placenta[J].Am J Physiol Regul Integr Comp Physiol, 2007, 293(5):R1809-R1822.
19. Guzmán-Gutiérrez E, Sandoval C, Nova E, et al.Differential expression of functional nucleoside transporters in non-differentiated and differentiated human endothelial progenitor cells[J].Placenta, 2010, 31(10):928-936.
20. Redzic ZB, Malatiali SA, Grujicic D, et al.Expression and functional activity of nucleoside transporters in human choroid plexus[J].Cerebrospinal Fluid Res, 2010, 7:2.
21. Perrone G, Morini S, Santini D, et al.Human equilibrative nucleoside transporter 1 and carcinoma of the ampulla of Vater:expression differences in tumour histotypes[J].Eur J Histochem, 2010, 54(3):e38.
22. Park JS, Hughes SJ, Cunningham FK, et al.Identification of cysteines involved in the effects of methanethiosulfonate reagents on human equilibrative nucleoside transporter 1[J].Mol Pharmacol, 2011, 80(4):735-746.
23. Procházková A, Liu S, Friess H, et al.Determination of 5-fluorouracil and 5-fluoro-2'-deoxyuridine-5'-monophosphate in pancreatic cancer cell line and other biological materials using capillary electrophoresis[J].J Chromatogr A, 2001, 916(1/2):215-224.
24. Mohelnikova-Duchonova B, Melichar B.Human equilibrative nucleoside transporter 1(hENT1):do we really have a new predictive biomarker of chemotherapy outcome in pancreatic cancer patients?[J].Pancreatology, 2013, 13(6):558-563.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of Human Equilibrative Nucleoside Transports on Cytotoxicity of 5-Fluorouracil in Breast Cancer Cells

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