Antileukemic activity of combined epigenetic agents, DNMT inhibitors zebularine and RG108 with HDAC inhibitors, against promyelocytic leukemia HL-60 cells
详细信息    查看全文
  • 作者:Jurate Savickiene (1)
    Grazina Treigyte (1)
    Veronika-Viktorija Borutinskaite (1)
    Ruta Navakauskiene (1)
  • 关键词:HL ; 60 ; Differentiation ; RG108 ; Zebularine ; HDAC inhibitors ; E ; cadherin ; Histones
  • 刊名:Cellular & Molecular Biology Letters
  • 出版年:2012
  • 出版时间:December 2012
  • 年:2012
  • 卷:17
  • 期:4
  • 页码:501-525
  • 全文大小:1590KB
  • 参考文献:1. Baylin, S.B., Herman, J.G., Graff, J.R., Vertino, P.M. and Issa, J.P. Alterations in DNA methylation: a fundamental aspect of neoplasia. Adv. Cancer Res. 72 (1998) 141鈥?96. CrossRef
    2. Toyota, M., Kopecky, K.J., Toyota, M.O., Jair, K.W., Willman, C.L. and Issa, J.P. Methylation profiling in acute myeloid leukemia. Blood 9 (2001) 2823鈥?829. CrossRef
    3. Paz, M.F., Fraga, M.F., Avila, S., Avila, S., Guo, M., Pollan, M., Herman, J.G. and Esteller, M. A systematic profile of DNA methylation in human cancer cell lines. Cancer Res. 63 (2003) 1114鈥?121.
    4. Teofilini, L., Martini, M., Luongo, M., Diverio, D., Capelli, G., Breccia, M., Lo Coco, F., Leone, G. and Larocca, L.M. Hypermethylation of CpG islands in the promoter region of p15 (INK4b) in acute promyelocytic leukemia represses p15 (INK4b) expression and correlates with poor prognosis. Leukemia 17 (2003) 919鈥?24. CrossRef
    5. Ekmekci, C.G., Guti茅rrez, M.I., Siraj, A.K., Ozbek, U. and Bhatia, K. Aberrant methylation of multiple tumor suppressor genes in acute myeloid leukemia. Am. J. Hematol. 77 (2004) 233鈥?40. CrossRef
    6. Mizuno, S., Chijiwa, T., Okamura, T., Akashi, K., Fukumaki, Y., Niho Y. and Sasaki, H. Expression of DNA methyltransferases DNMT1, 3A, and 3B in normal hematopoiesis and in acute and chronic myelogenous leukemia. Blood 97 (2001) 1172鈥?179. CrossRef
    7. Silverman, L.R., Holland, J.F., Weinberg, R.S., Alter, B.P., Davi, R.B., Ellison, R.R., Demakos, E.P., Cornell, C.J. Jr., Carey, R.W. and Schiffer, C. Effect of treatment with 5-aza cytidine on the / in vivo and / in vitro hematopoiesis in patients with myelodysplastic syndromes. Leukemia 7 (1993) 21鈥?9.
    8. Issa, J.P., Garcia-Manero, G., Giles, F.J., Mannari, R., Thomas, D., Faderl, S., Bayar, E., Lyons, J., Rosenfeld, C., Cortes, J. and Kantarjian, H.M. Phase I study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2鈥?deoxycytidine (decitabine) in hematopoietic malignancies. Blood 103 (2004) 1635鈥?640. CrossRef
    9. Bug, G. and Ottmann, O.G. The HDAC system and association with acute leukemias and myelodysplastic syndromes. Invest. New Drugs 28Suppl 1 (2010) S36鈥?9. CrossRef
    10. Cashen, A.F., Schiller, G.J., O鈥橠onnell, M.R. and DiPersio, J.F. Multicenter, phase II study of decitabine for the first-line treatment of older patients with acute myeloid leukemia. J. Clin. Oncol. 28 (2010) 556鈥?61. CrossRef
    11. M眉ller, S. and Kr盲mer, O.H. Inhibitors of HDACs-effective drugs against cancer? Curr. Cancer Drug Targets 10 (2010) 210鈥?28. CrossRef
    12. Kim, C.H., Marquez, V.E., Mao, D.T., Haines, D.R. and McCormack, J.J. Synthesis of pyrimidin-2-one nucleosides as acid-stable inhibitors of cytidine deaminase. J. Med. Chem. 29 (1986) 1374鈥?380. CrossRef
    13. Hurd, P.J., Whitmarsh, A.J., Baldwin, G.S., Kelly, S.M., Waltho, J.P., Price, N.C., Connolly, B.A. and Hornby, D.P. Mechanism-based inhibition of C5-cytosine DNA methyltransferases by 2-H pyrimidone. J. Mol. Biol. 286 (1999) 389鈥?01. CrossRef
    14. Zhou, L., Cheng, X., Connolly, B.A., Dickman, M.J., Hurd, P.J. and Hornby, D.P. Zebularine: a novel DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases. J. Mol. Biol. 23 (2002) 581鈥?99.
    15. Cheng, J.C., Matsen, C.B., Gonzales, F.A., Ye, W., Greer, S., Marquez, V.E., Jones, P.A. and Selker, E.U. Inhibition of DNA methylation and reactivation of silenced genes by zebularine. J. Natl. Cancer Inst. 95 (2003) 399鈥?09. CrossRef
    16. Marquez, V.E., Kelly, J.A., Agbaria, R., Ben-Kasus, T., Cheng, J.C., Yoo, C.B. and Jones, P.A. Zebularine: a unique molecule for an epigenetically based strategy in cancer chemotherapy. Ann. N. Y. Acad. Sci. 1008 (2005) 246鈥?54. CrossRef
    17. Cheng, J.C., Weisenberger, D.J., Gonzales, F.A., Liang, G., Xu, G.L., Hu, Y.G., Marquez, V.E. and Jones P.A. Continuous zebularine treatment effectively sustains demethylation in human bladder cancer cells. Mol. Cell Biol. 24 (2004) 1270鈥?278. CrossRef
    18. Scott, S.A., Lakshimikuttysamma, A., Sheridan, D.P., Sanche, S.E., Geyer, C.R. and DeCoteau, J.F. Zebularine inhibits human myeloid leukemia cell growth in vitro in association with p15INK4B demethylation and reexpression. Exp. Hematol. 35 (2007) 263鈥?73. CrossRef
    19. Veerla, S., Panagopoulos, I., Jin, Y., Lindgren, D. and H枚glund, M. Promoter analysis of epigenetically controlled genes in bladder cancer. Genes Chromosomes Cancer 47 (2008) 368鈥?78. CrossRef
    20. Brueckner, B., Boy, R.G., Siedlecki, P., Musch, T., Kliem, H.C., Zielenkiewicz, P., Suhai, S., Wiessler, M. and Lyko, F. Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferases. Cancer Res. 65 (2005) 6305鈥?311. CrossRef
    21. Tsai, H.-C. and Baylin, S.B. Cancer epigenetics: linking basic biology to clinical medicine. Cell. Res. 21 (2011) 502鈥?17. CrossRef
    22. Cameron, E.E., Bachman, K.E., Myohanen, S., Herman, J.G. and Baylin, S.B. Synergy of demethylation and histone deacetylase inhibition in the reexpression of genes silenced in cancer. Nat. Genet. 21 (1999) 103鈥?07. CrossRef
    23. Gore, S.D., Baylin, S., Sugar, E., Carraway, H., Miller, C.B., Carducci, M., Grever, M., Galm, O., Dauses, T., Karp, J.E., Rudek, M.A., Zhao, M., Smith, B.D., Manning, J., Jiemjit, A., Dover, G., Mays, A., Zwiebel, J., Murgo, A., Weng, L.J. and Herman, J.G. Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms. Cancer Res. 66 (2006) 6361鈥?369. CrossRef
    24. Blum, W., Klisovic., R.B., Hackanson., B., Liu, Z., Liu, S., Devine, H., Vukosavljevic, T., Huynh, L., Lozanski, G., Kefauver, C., Plass, C., Devine, S.M., Heerema, N.A., Murgo, A., Chan, K.K., Grever, M.R., Byrd, J.C. and Marcucci, G. Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia. J. Clin. Oncol. 25 (2007) 3884鈥?891. CrossRef
    25. Herman, J., Merlo, J.J. and Baylin, S.B. Hypermethylation-associated inactivation indicates a tumor suppressor role for p15 INK4b. Cancer Res. 56 (1996) 722鈥?27.
    26. Herman, J.G., Civin, C.I., Issa, J.P., Collector, M.I., Sharkis, S.J. and Baylin, S.B. Distinct patterns of inactivation of p15INK4B and p16INK4A characterize the major types of hematological malignancies. Cancer Res. 57 (1997) 837鈥?41.
    27. Cameron, E.E., Baylin, S.B. and Herman, J.G. p15INK4B CpG island methylation in primary acute leukemia is heterogeneous and suggests density as a critical factor for transcriptional silencing. Blood 94 (1999) 2445鈥?451.
    28. Oki, Y. and Issa, J.P. Epigenetic mechanisms in AML-a target for therapy. Cancer Treat. Res. 145 (2010) 19鈥?0. CrossRef
    29. Ribeiro-Filho, L.A., Franks, J., Sasaki, M., Shiina, H., Li, L.C., Nojima, D., Arap, S., Carroll, P., Enokida, H., Nakagawa, M., Yonezawa, S. and Dahiya, R. CpG hypermethylation of promoter region and inactivation of E-cadherin gene in human bladder cancer. Mol. Carcinog. 34 (2002) 187鈥?98. CrossRef
    30. Corn, P.G., Smith, B.D., Ruckdeschel, E.S., Douglas, D., Baylin, S.B. and Herman, J.G. E-cadherin expression is silenced by 5鈥睠pG island methylation in acute myeloid leukemia. Clin. Cancer Res. 6 (2000) 4243鈥?248.
    31. Melki, J.R., Vincent, P.C., Brown, R.D. and Clark, S.J. Hypermethylation of E-cadherin in leukemia. Blood 95 (2000) 3208鈥?213.
    32. Shimamoto, T., Ohyashiki, J.H. and Ohyashiki, K. Methylation of / p15 (INK4b) and / E-cadherin genes is independently correlated with poor prognosis in acute myeloid leukemia. Leuk. Res. 6 (2005) 653鈥?59. CrossRef
    33. Farinha, N.J., Shaker, S., Lemaire, M., Momparler, L., Bernstein, M. and Momparler, R.L. Activation of expression of p15, p73 and E-cadherin in leukemic cells by different concentrations of 5-aza-2鈥?deoxycytidine (Decitabine). Anticancer Res. 24 (2004) 75鈥?8.
    34. Collins, S. The HL-60 promyelocytic leukemia cell line: proliferation, differentiation and cellular oncogene expression. Blood 70 (1987) 1233鈥?244.
    35. Hurley, C.K. Electrophoresis of histones: a modified Panyim and Chalkley system for slab gels. Anal. Biochem. 80 (1977) 624鈥?26. CrossRef
    36. Nayera, H., El-Shakankiry, M.D., Ghada, I. and Mossallam, M.D. p15 (INK4B) and E-cadherin CpG Island methylation is frequent in Egyptian acute myeloid leukemia. J. Egypt. Nat. Cancer Inst. 18 (2006) 227鈥?32.
    37. Chuang, J.C., Yoo, C.B., Kwan, J.M., Li, T.W., Liang, G., Yang, A.S. and Jones, P.A. Comparison of biological effects of non-nucleoside DNA methylation inhibitors versus 5-aza-2鈥?deoxycytidine. Mol. Cancer Ther. 4 (2005) 1515鈥?520. CrossRef
    38. Stressemann, C., Brueckner, B., Musch, T., Stopper, H. and Lyko, F. Functional diversity of DNA methyltransferase inhibitors in human cancer cell lines. Cancer Res. 66 (2006) 2794鈥?800. CrossRef
    39. Flotho, C., Claus, R., Batz, C., Schneider, M., Sandrock, I., Inhde, S., Plass, C., Niemeyer, C.M. and Lubbert, M. The DNA methyltransferase inhibitors azacytidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia 23 (2009) 1019鈥?028. CrossRef
    40. Ben-Kausus, T., Ben-Zvi, Z., Marquez, V.E., Kelly, J.A. and Agbaria, R. Metabolic activation of zebularine, a novel DNA methylation inhibitor, in human bladder carcinoma cells. Biochem. Pharmacol. 70 (2005) 121鈥?33. CrossRef
    41. Lemaire, M., Momparlier, L.F., Bernstein, M.L., Marquez, V.E. and Momparlier, R.L. Enhancement of antineoplastic action of 5-aza-2鈥?deoxycytidine by zebularine on L1210 leukemia. Anticancer Drugs 16 (2005) 301鈥?08. CrossRef
    42. Cheng, C.C., Yoo, C.B., Weisenberg, D.J., Chuang, J., Wozniak, C., Liang, G., Marquez, V.E., Greer, S., Orntoft, T.F., Thykjaer, T. and Jones, P.A. Preferential response of cancer cells to zebularine. Cancer Cell 6 (2004) 151鈥?58. CrossRef
    43. Gotz, C., Wagner, P., Issinger, O.G. and Montenarh, M. p21WAF1/CIP 1 interacts with protein kinase CK2. Oncogene 13 (1996) 391鈥?98.
    44. Waga, S., Hannon, G.J., Beach, D. and Stillman, B. The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature 369 (1994) 1766鈥?771.
    45. Chuang, L.S., Ian, H.I., Koh, T.W., Ng, H.H., Xu, G. and Li, B.F. Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21 Waf1. Science 277 (1996) 2000.
    46. Velicesku, M., Weisenberger, D.J., Gonzales, F.A., Tsai, Y.C., Nguen, C.T. and Jones, P.A. Cell division is required for de novo methylation of CpG islands in bladder cancer. Cancer Res. 62 (2002) 2378鈥?384.
    47. Millutinovic, S., Zhuang, Q., Niveleu, A. and Szyf, M. Epigenomic stress response. Knockdown of DNA methyltransferase 1 triggers an intra-S-phase arrest of DNA replication and induction of stress response genes. J. Biol. Chem. 278 (2003) 14985鈥?4995. CrossRef
    48. Billam, M., Sobolewski, M.D. and Davidson, N.E. Effects of a novel DNA methyltransferase inhibitor zebularine on human breast cancer cells. Breast Cancer Res. Treat. 120 (2010) 581鈥?92. CrossRef
    49. Nieto, M., Sampler, E., Fraga, M.F., Gonzales de Buitrago, G., Esteller, M. and Serrano, M. The absence of p53 is critical for the induction of apoptosis by 5-aza-2鈥?cytidine. Oncogene 3 (2004) 735鈥?43. CrossRef
    50. Neureither, D., Zopf, S., Leu, T., Dietze, O., Hauser-Kronberger, C., Hahn, E.G., Herold, C. and Ocker, M. Apoptosis, proliferation and differentiation patterns are influenced by zebularine and SAHA in pancreatic cancer models. Scand. J. Gastroenterol. 42 (2007) 103鈥?16. CrossRef
    51. Savickiene, J., Treigyte, G., Jonusiene, V., Bruzaite, R., Borutinskaite, V.-V. and Navakauskiene, R. Epigenetic changes by zebularine leading to enhanced differentiation of human promyelocytic leukemia NB4 and KG1 cells. Mol. Cell. Biochem. 359 (2012) 245鈥?61. CrossRef
    52. Martin, S.J., Bradley, G.J. and Cotter, T.G. HL-60 cells induced differentiate towards neutrophils subsequently die via apoptosis. Clin. Exp. Immunol. 79 (1990) 448鈥?53. CrossRef
    53. Nagy, I., Thomazy, V.A., Shipley, G.L., Fesus, L., Lamph, W., Heyman, R.A., Chandraratana, R.A. and Davies, P.I. Activation of retinoid X receptors induces apoptosis in HL-60 cell line. Mol. Cell Biol. 15 (1995) 3440鈥?451.
    54. Watson, R.W., Rostein, O.D., Parodo, J., Bitar, R., Hackman, D. and Marshall, J.C. Granulocytic differentiation of HL-60 cells result in spontaneous apoptosis mediated by increased caspase expression. FEBS Letters 412 (1997) 603鈥?09. CrossRef
    55. Ozeki, M. and Shively, J.E. Differential cell fates induced by all-trans retinoic acid-treated HL-60 human leukemia cells. J. Leuk. Biol. 84 (2008) 769鈥?79. CrossRef
    56. Ueno, H., Kizaki, M., Matsushita, H., Muto, A., Yamato, K., Nishihara, T., Hid, T., Yoshimura, H., Koeffler, H.P., Ikeda, Y. A novel retinoic acid receptor (RAR)-selective antagonist inhibits differentiation and apoptosis of HL-60 cells: implications of RAR伪-mediated signals in myeloid leukemic cells. Leuk. Res. 6 (1998) 517鈥?25. CrossRef
    57. De The, H., Lavau, C., Marchio, A., Chomienne, C., Degos, L. and Dejean, A. A PML-RAR伪 fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR. Cell 66 (1991) 675鈥?84. CrossRef
    58. Altucci, L., Rossin, A., Raffelsberger, W., Reitmair, A., Chomienne, C. and Gronemeyer, H. Retinoic acid-induced apoptosis in leukemia cells is mediated by paracrine action of tumor-selective death ligand TRAIL. Nat. Med. 7 (2001) 680鈥?86. CrossRef
    59. Benoit, G.R., Flexor, M., Besan莽on, F., Altucci, L., Rossin, A., Hillion, J., Balajthy, Z., Legres, L., S茅gal-Bendirdjian, E., Gronemeyer, H. and Lanotte, M. Autonomous rexinoid death signaling is suppressed by converging signaling pathways in immature leukemia cells. Mol. Endocrinol. 15 (2011) 1154鈥?189. CrossRef
    60. Rao, S.P., Rechhsteiner, M.P., Berger, C., Sigrist, J.A., Nadal, D. and Bernaqsconi, M. Zebularine reactivates silenced E-cadherin but unlike 5-Azacytidine does not induce switching from latent to lytic Epstein-Barr virus infection in Burkit lymphoma Akata cells. Mol. Cancer 6 (2007) 3鈥?. CrossRef
    61. Fazi, F., Travaglini, L., Carotti, D., Palitti, F., Diverio, D., Alcalay, M., McNamara, S., Miller, W.H.Jr., Lo Coco, F., Pelicci, P.G. and Nervi, C. Retinoic acid targets DNA-methyltransferases and histone deacetylases during APL blast differentiation in vitro and in vivo. Oncogene 24 (2005) 1820鈥?830. CrossRef
    62. Griffiths, E.A. and Gore, S.D. DNA methyltransferase and histone deacetyase inhibitors in the treatment of myelodysplastic syndromes. Semin. Hematol. 45 (2008) 23鈥?0. CrossRef
    63. Savickiene, J., Borutinskaite, V.-V., Treigyte, G., Magnusson, K.-E. and Navakauskiene, R. The novel deacetylase inhibitor BML-210 exerts growth inhibitory, proapoptotic and differentiation stimulating effects on the human leukemia cell lines. Europ. J. Pharmacol. 549 (2006) 9鈥?8. CrossRef
    64. Bradbury, C.A., Khanim, F.L., Hayden, R., Bunce, C.M., White, D.A., Drayson, M.T., Craddock, C. and Turner, B.M. Histone deacetylases in acute myeloid leukemia show a distinct pattern of expression that changes selectively in response to deacetylase inhibitors. Leukemia 19 (2005) 1751鈥?759. CrossRef
    65. Wada, T., Kikuchi, J., Nishimura, N., Shimizu, R., Kitamura, T. and Furukawa, Y. Expression levels of histone deacetylases determine the cell fate of hematopoietic progenitors. J. Biol. Chem. 28 (2009) 3073鈥?069.
    66. Kr盲mer, O.H., Zhu, P., Ostendorff, H.P., Golebiewski, M., Tiefenbach, J., Peters, M.A., Brill, B., Groner, B., Bach, I., Heinzel, T. and G枚ttlicher, M. The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2. EMBO J. 22 (2003) 3411鈥?420. CrossRef
    67. Gozzini, A., Rovida, E., Sbarba, P.D., Galimbert, S. and Santini, V. Butyrates, as a single drug, induce histone acetylation and granulocytic maturation: possible selectivity on core binding factor-acute myeloid leukemia blasts. Cancer Res. 15 (2003) 8955鈥?961.
    68. Peinado, H., Ballestar, E., Esteller, M. and Cano, A. Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex. Mol. Cell Biol. 24 (2004) 306鈥?19. CrossRef
    69. Von Burstin, J., Eser, S., Paul, M.C., Seidler, B., Brandl, M., Messer, M., von Waerder, A., Schmit, A., Mages, J., Pagel, P., Schnieke, R.M., Schneider, G. and Saur, D. E-cadherin regulates metastasis of pancreatic cancer in vivo and is suppressed by a SNAIL/HDAC1/HDAC2 repressor complex. Gastroenterology 137 (2009) 361鈥?71. CrossRef
    70. Grunstein, M. Histone acetylation in chromatin structure and transcription. Nature 389 (1997) 349鈥?52. CrossRef
    71. Strahl, B.D. and Allis, D. The language of covalent histone modifications. Nature 403 (2000) 41鈥?5. CrossRef
    72. Kouzarides, T. Histone methylation in transcriptional control. Curr. Opin. Genet. Dev. 12 (2002) 198鈥?09. CrossRef
    73. Thomson, S., Clayton, A. L. and Mahadevan, L.C. Independent dynamic regulation of histone phosphorylation and acetylation during immediateearly gene induction. Mol. Cell 8 (2001) 1231鈥?241. CrossRef
    74. Nightingale, K.P., Gendreizig, S., White, D.A., Bradbury, C., Hollfelder, F. and Turner, B.M. Cross-talk between histone modifications in response to histone deacetylase inhibitors. J. Biol. Chem. 282 (2007) 4408鈥?416. CrossRef
    75. El-Osta, A., Kandharidis, P., Zalcberg, J.R. and Wolffe, A.P. Precipitous release of methyl-CpG binding protein 2 and histone deacetylase 1 from the methylated human multidrug resistance gene (MDR1) on activation. Mol. Cell Biol. 22 (2002) 1844鈥?857. CrossRef
  • 作者单位:Jurate Savickiene (1)
    Grazina Treigyte (1)
    Veronika-Viktorija Borutinskaite (1)
    Ruta Navakauskiene (1)

    1. Department of Molecular Cell Biology, Institute of Biochemistry, Vilnius University, Mokslinink懦 12, Vilnius, LT, 08662, Lithuania
文摘
DNMT inhibitors are promising new drugs for cancer therapies. In this study, we have observed the antileukemic action of two diverse DNMT inhibitors, the nucleoside agent zebularine and the non-nucleoside agent RG108, in human promyelocytic leukemia (PML) HL-60 cells. Zebularine but not RG108 caused dose- and time-dependent cell growth inhibition and induction of apoptosis. However, co-treatment with either drug at a non-toxic dose and all trans retinoic acid (RA) reinforced differentiation to granulocytes, while 24 or 48 h-pretreatment with zebularine or RG108 followed by RA alone or in the presence of HDAC inhibitors (sodium phenyl butyrate or BML-210) significantly accelerated and enhanced cell maturation to granulocytes. This occurs in parallel with the expression of a surface biomarker, CD11b, and early changes in histone H4 acetylation and histone H3K4me3 methylation. The application of both drugs to HL-60 cells in continuous or sequential fashion decreased DNMT1 expression, and induced E-cadherin promoter demethylation and reactivation at both the mRNA and the protein levels in association with the induction of granulocytic differentiation. The results confirmed the utility of zebularine and RG108 in combinations with RA and HDAC inhibitors to reinforce differentiation effects in promyelocytic leukemia.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700