Silencing of Her2, CCNB1 and pKC Genes by siRNA Results in Prolonged Retardation of Neuroblastoma Cell Division

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Deregulation of the expression of the genes that are involved in the control of the cell cycle impairs cellular differentiation and leads to cell death. This process can result in uncontrollable cell proliferation and, subsequently, cancer development. In this study, we examined the effect of the silencing of cancer-related genes by small interfering RNAs (siRNA) targeted at mRNA of Her2, cyclin B1 (CCNB1), and protein kinase C (PKC) on the proliferation of human cancer cells of different origins. Maximum silencing of CCNB1, Her2 (in KB-3-1, SK-N-MC, MCF-7 cells), and PKC (in MCF-7 cells) was achieved 72 h after transfection of the corresponding siR-NAs, and 12 days after the transfection, the initial levels of the target mRNAs were fully recovered. Silencing of Her2, CCNB1, and PKC differently effected the proliferation of the cell lines under study. The most pronounced antiproliferative action of the investigated siRNAs was observed in neuroblastoma SK-N-MC cells (3 - 10-fold reduction in the proliferation rate) even after the recovery of the initial levels of expression of the Her2, CCNB1, and PKC genes. The obtained data indicate that the CCNB1 and PKC genes can be used as targets in the development of drugs for neuroblastoma treatment.

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Silencing of Her2, CCNB1 and pKC Genes by siRNA Results in Prolonged Retardation of Neuroblastoma Cell Division

About the authors

I A Akimov

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

E L Chernolovskaya

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences


Yu E Spitsyna

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

E I Ryabchikova

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

M A Zenkova

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences


  1. Sulic S., Panic L., Dikic I., Volarevic S. // Croat. Med. J. 2005. V. 46. P. 622-638.
  2. Sandhu C., Slingerland J. // Cancer Detect. Prev. 2000. V. 24. P. 107-118.
  3. Malumbres M., Hunt S.L., Sotillo R., Martin J., Odajima J., Martin A., Dubus P., Ortega S., Barbacid M. // Adv. Exp. Med. Biol. 2003. V. 532. P. 1-11.
  4. Yuan J.P., Yan R.L., Kramer A., Eckerdt F., Roller M., Kaufmann M., Strebhardt K. // Oncogene. 2004. V. 23. P. 5843-5852.
  5. Minana M.D., Felipo V., Cortes F., Grisolia S. // FEBS Lett. 1991. V. 284. P. 60-62.
  6. Wu T.T., Hsieh Y.H., Hsieh Y.S., Liu J.Y. // J. Cell. Biochem. 2008. V. 103. P. 9-20.
  7. Faltus T., Yuan J.P., Zimmer B., Kramer A., Loibl S., Kaufmann M., Strebhardt K. // Neoplasia. 2004. V. 6. P. 786-795.
  8. Vermeulen K., van Bockstaele D.R., Berneman Z.N. // Cell Prolif. 2003. V. 36. P. 131-149.
  9. Tuschl T. // Chembiochem. 2001. V. 2. P. 239-245.
  10. Tabara H., Grishok A., Mello C.C. // Science. 1998. V. 282. P. 430-431.
  11. Elbashir S.M., Harborth J., Lendeckel W., Yalcin A., Weber K., Tuschl T. // Nature. 2001. V. 411. P. 494-498.
  12. Yarden Y. // Oncology. 2001. V. 61. P. 1-13.
  13. Nishizuka Y. // Nature. 1984. V. 308. P. 693-698.
  14. Ali A.S., Ali S., El-Rayes B.F., Philip P.A., Sarkar F.H. // Cancer Treat. Rev. 2009. V. 35. P. 1-8.
  15. Robert N.J., Favret A.M. // Hematol. Oncol. Clin. North Am. 2007. V. 21. P. 293-302.
  16. Meric F., Hung M.C., Hortobagyi G.N., Hunt K.K. // J. Am. Coll. Surg. 2002. V. 194. P. 488-501.
  17. Aaltonen K., Amini R.M., Heikkila P., Aittomaki K., Tamminen A., Nevanlinna H., Blomqvist C. // Br. J. Cancer. 2009. V. 100. P. 1055-1060.
  18. Koivunen J., Aaltonen V., Peltonen J. // Cancer Lett. 2006. V. 235. P. 1-10.
  19. Martiny-Baron G., Fabbro D. // Pharmacological Res. 2007. V. 55. P. 477-486.
  20. Revillion F., Bonneterre J., Peyrat J.P. // Eur. J. Cancer. 1998. V. 34. P. 791-808.
  21. Williams T.M., Weiner D.B., Greene M.I., Maguire H.C. // Pathobiology. 1991. V. 59. P. 46-52.
  22. Wright C., Angus B., Nicholson S., Sainsbury J.R., Cairns J., Gullick W.J., Kelly P., Harris A.L., Horne C.H. // Cancer Res. 1989. V. 49. P. 2087-2090.
  23. Tandon A.K., Clark G.M., Chamness G.C., Ullrich A., Mcguire W.L. // J. Clin. Oncol. 1989. V. 7. P. 1120-1128.
  24. Slamon D. J., Clark G.M., Wong S.G., Levin W. J., Ullrich A., Mcguire W.L. // Science. 1987. V. 235. P. 177-182.
  25. Gulati S., Ytterhus B., Granli U.S., Gulati M., Lydersen S., Torp S.H. // Diagn. Pathol. 2010. V. 5. P. 18-26.
  26. Soria J.C., Jang S.J., Khuri F.R., Hassan K., Lin D., Hong W.K., Mao L. // Cancer Res. 2000. V. 60. P. 4000-4004.
  27. Yasuda M., Takesue F., Inutsuka S., Honda M., Nozoe T., Korenaga D. // J. Cancer Res. Clin. Oncol. 2002. V. 128. P. 412-416.
  28. Song Y.M., Zhao C.L., Dong L.J., Fu M., Xue L., Huang Z., Tong T., Zhou Z., Chen A., Yang Z., et al. // Carcinogenesis. 2008. V. 29. P. 307-315.
  29. Berchuck A., Rodriguez G., Kinney R.B., Soper J.T., Dodge R.K., Clarkepearson D.L., Bast R.C. // Am. J. Obstet. Gynecol. 1991. V. 164. P. 15-21.
  30. Berchuck A., Kamel A., Whitaker R., Kerns B., Olt G., Kinney R., Soper J.T., Dodge R., Clarke-Pearson D.L., Marks P., et al. // Cancer Res. 1990. V. 50. P. 4087-4091.
  31. Marks J.R., Humphrey P.A., Wu K., Berry D., Bandarenko N., Kerns B.J.M., Iglehart J.D. // Ann. Surg. 1994. V. 219. P. 332-341.
  32. Carr J.A., Havstad S., Zarbo R.J., Divine G., Mackowiak P., Velanovich V. // Arch. Surg. 2000. V. 135. P. 1469-1474.
  33. Casalini P., Iorio M.V., Galmozzi E., Menard S. // J. Cell. Physiol. 2004. V. 200. P. 343-350.
  34. Yamamoto T., Ikawa S., Akiyama T., Semba K., Nomura N., Miyajima N., Saito T., Toyoshima K. // Nature. 1986. V. 319. P. 230-234.
  35. Pines J., Hunter T. // Ciba Fdn. Symp. 1992. V. 170. P. 187-204.
  36. Sutherland R.L., Watts C.K.W., Musgrove E.A. // J. Steroid Biochem. Mol. Biol. 1993. V. 47. P. 99-106.
  37. Gomez L.A., de las Pozas A., Reiner T., Burnstein K., Perez-Stable C. // Mol. Cancer Ther. 2007. V. 6. P. 1534-1543.
  38. Sarafan-Vasseur N., Lamy A., Bourguignon J., Le Pessot F., Hieter P., Sesboüé R., Bastard c., Frébourg T., Flaman J.M. // Oncogene. 2002. V. 21. P. 2051-2057.
  39. Newton A.C. // Chem. Rev. 2001. V. 101. P. 2353-2364.
  40. Clemens M.J., Trayner I., Menaya J. // J. Cell Sci. 1992. V. 103. P. 881-887.
  41. Akimov I.A., Chernolovskaya E.L. // Mol. Biol. 2010. V. 44. P. 89-96.
  42. Amarzguioui M., Rossi J. J., Kim D. // FEBS Lett. 2005. V. 579. P. 5974-5981.
  43. Hohjoh H. // FEBS Lett. 2004. V. 557. P. 193-198.
  44. Matveeva O., Nechipurenko Y., Rossi L., Moore B., Saetrom P., Ogurtsov A.Y., Atkins J.F., Shabalina S.A. // Nucl. Acids Res. 2007. V. 35. P. 1-10.
  45. Chattopadhyay N., Kher R., Godbole M. // Biotechniques. 1993. V. 15. P. 24-26.
  46. Carmichael J., Degraff W.G., Gazdar A.F., Minna J.D., Mitchell J.B. // Cancer Res. 1987. V. 47. P. 936-942.
  47. Pearse E. Gistokhimia (Histochemistry). Moscow: Inostrannaya literatura, 1962. 962 p.
  48. Castanotto D., Rossi J. J. // Nature. 2009. V. 457. P. 426-433.
  49. Choudhury A., Charo J., Parapuram S.K., Hunt R.C., Hunt D.M., Seliger B., Kiessling R. // Int. J. Cancer. 2004. V. 108. P. 71-77.
  50. Blankinship M.J., Gregorevic P., Chamberlain J.S. // Mol. Ther. 2006. V. 13. P. 241-249.
  51. Gao G.P., Wilson J.M., Wivel N.A. // Adv. Virus Res. 2000. V. 55. P. 529-543.
  52. Snyder R.O., Flotte T.R. // Curr. Opin. Biotechnol. 2002. V. 13. P. 418-423.
  53. Choi M.S., Yuk D.Y., Oh J.H., Jung H.Y., Han S.B., Moon D.C., Hong J.T. // Anticancer Res. 2008. V. 28. P. 3777-3784.

Copyright (c) 2011 Akimov I.A., Chernolovskaya E.L., Spitsyna Y.E., Ryabchikova E.I., Zenkova M.A.

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