surgoncoКреативная хирургия и онкологияCreative surgery and oncology2076-30932307-0501Башкирский государственный медицинский университет10.24060/2076-3093-2014-0-4-69-75surgonco-76Research ArticleОБЗОРЫ ЛИТЕРАТУРЫREVIEWТРАНСКРИПЦИОННЫЙ ФАКТОР NF-KB КАК ТЕРАПЕВТИЧЕСКАЯ МИШЕНЬ В ЛЕЧЕНИИ ЗЛОКАЧЕСТВЕННЫХ ОПУХОЛЕЙTHE TRANSCRIPTION FACTOR NF-KB AS A THERAPEUTIC TARGET IN THE TREATMENT OF MALIGNANT TUMORSУмезаваК.UmezawaK.

зав. кафедрой молекулярного скрининга мишеней лекарственных средств Медицинского университета Айчи, профессор

prfg@mail.ruГанцевШ. Х.GantsevSh. Kh.

директор НИИО БГМУ, д-р мед. наук, профессор

prfg@mail.ruКзыргалинШ. Р.KzyrgalinSh. R.

научный сотрудник НИИО БГМУ

prfg@mail.ruЯмидановР. С.YamidanovR. S.

научный сотрудник НИИО БГМУ, канд. биол. наук

prfg@mail.ruГанцевК. Ш.GantsevK. Sh.

научный сотрудник НИИО БГМУ, д-р мед. наук, профессор

prfg@mail.ruАмировР. А.AmirovR. A.

менеджер инновационных проектов НИИО БГМУ

prfg@mail.ruЛогиноваМ. В.LoginovaM. V.

научный сотрудник НИИО БГМУ

prfg@mail.ruУниверситет Айчи, г. Токио, ЯпонияЯпонияAichi University, Tokyo, JapanJapanГБОУ ВПО Башкирский государственный медицинский университет, научно-исследовательский институт онкологии БГМУ, г. УфаРоссияBashkir State Medical University, Scientific Research Institute of Oncology, UfaRussian Federation201426012017046975Copyright © Умезава К., Ганцев Ш.Х., Кзыргалин Ш.Р., Ямиданов Р.С., Ганцев К.Ш., Амиров Р.А., Логинова М.В., 20172017Умезава К., Ганцев Ш.Х., Кзыргалин Ш.Р., Ямиданов Р.С., Ганцев К.Ш., Амиров Р.А., Логинова М.В.Umezawa K., Gantsev S.K., Kzyrgalin S.R., Yamidanov R.S., Gantsev K.S., Amirov R.A., Loginova M.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.surgonco.ru/jour/article/view/76

Транскрипционный фактор NF-kB играет ключевую роль в различных физиологических процессах, таких как иммунный ответ, клеточная пролиферация, клеточный апоптоз и воспаление. Контролируя транскрипционную активность множества генов, ответственных за различные пути воспалительных и злокачественных процессов, NF-kB вовлечен в широкий спектр заболеваний. Отдельного внимания заслуживает участие сигнальных путей, регулируемых NF-kB, в канцерогенезе, ангиогенезе, в том числе и в устойчивости опухолей к химио- и радиотерапии. Сочетание онкологических и воспалительных процессов, сопровождающихся конститутивной активацией NF-kB, делает его одной из перспективных мишеней направленного фармакологического воздействия при терапии рака.

The transcription factor NF-kB plays a key role in various physiological processes such as immune response, cell proliferation, cell apoptosis and inflammation. Controlling the transcriptional activity of a number of genes responsible for different ways of inflammatory processes and of malignant, NF-kB is involved in a wide range of diseases. Special attention deserves part signalnych paths controlled NF-kB, in carcinogenesis, angiogenesis, including tumor and stability to chemotherapy and radiotherapy. The combination of cancer and inflammatory processes involving constitutive activation of NF-kB, making it a promising target for pharmacological intervention aimed at cancer therapy.

NF-kBраклечениеNF-kBcancertreatmentReferencesAhmad R., Raina D., Trivedi V., Ren J., Rajabi H., Kharbanda S., Kufe D. MUC1 oncoprotein activates the IkappaB kinase beta complex and constitutive NF-kappaB signaling // Nat. Cell Biol. – 2007. – Vol. 9. – P. 1419-1427.Ahmad R., Raina D., Trivedi V., Ren J., Rajabi H., Kharbanda S., Kufe D. MUC1 oncoprotein activates the IkappaB kinase beta complex and constitutive NF-kappaB signaling // Nat. Cell Biol. – 2007. – Vol. 9. – P. 1419-1427.Ahmed K.M., Cao N., Li J.J. HER-2 and NF-kappaB as the targets for therapy-resistant breast cancer // Anticancer Res. – 2006. – Vol. 26. – №6В. – P. 4235-4243.Ahmed K.M., Cao N., Li J.J. HER-2 and NF-kappaB as the targets for therapy-resistant breast cancer // Anticancer Res. – 2006. – Vol. 26. – №6В. – P. 4235-4243.Basseres D.S., Baldwin A.S. Nuclear factor-kappaB and inhibitor of kappaB kinase pathways in oncogenic initiation and progression // Oncogene. – 2006. – Vol. 25. – P. 6817-6830.Basseres D.S., Baldwin A.S. Nuclear factor-kappaB and inhibitor of kappaB kinase pathways in oncogenic initiation and progression // Oncogene. – 2006. – Vol. 25. – P. 6817-6830.Beck B., Blanpain C. Unravelling cancer stem cell potential // Nat. Rev. Cancer. – 2013. –№10. – P. 727-738.Beck B., Blanpain C. Unravelling cancer stem cell potential // Nat. Rev. Cancer. – 2013. –№10. – P. 727-738.Burstein E., Duckett C.S. Dying for NF-kappaB? Control of cell death by transcriptional regulation of the apoptotic machinery // Curr.Opin. Cell Biol. – 2003. – Vol. 15. – P. 732-737.Burstein E., Duckett C.S. Dying for NF-kappaB? Control of cell death by transcriptional regulation of the apoptotic machinery // Curr.Opin. Cell Biol. – 2003. – Vol. 15. – P. 732-737.Cilloni D., Martinelli G., Messa F., Baccarani M., Saglio G. Nuclear factor kB as a target for new drug development in myeloid malignancies // Haematologica. – 2007. – Vol. 92. – P. 1224-1229.Cilloni D., Martinelli G., Messa F., Baccarani M., Saglio G. Nuclear factor kB as a target for new drug development in myeloid malignancies // Haematologica. – 2007. – Vol. 92. – P. 1224-1229.De Souza P.L., Castillo M., Myers C.E. Enhancement of paclitaxel activity against hormone-refractory prostate cancer cells in vitro and in vivo by quinacrine // Br. J. Cancer. – 1997. – Vol. 75. – №11. – P. 1593-1600.De Souza P.L., Castillo M., Myers C.E. Enhancement of paclitaxel activity against hormone-refractory prostate cancer cells in vitro and in vivo by quinacrine // Br. J. Cancer. – 1997. – Vol. 75. – №11. – P. 1593-1600.DeAlmagro M.C., Vucic D. The inhibitor of apoptosis (IAP) proteins are critical regulators of signaling pathways and targets for anti-cancer therapy // Exp. Oncol. – 2012. – Vol. 34. – №3. – P. 200-211.DeAlmagro M.C., Vucic D. The inhibitor of apoptosis (IAP) proteins are critical regulators of signaling pathways and targets for anti-cancer therapy // Exp. Oncol. – 2012. – Vol. 34. – №3. – P. 200-211.Dong Z., Nemeth J.A., Cher M.L., Palmer K.C., Bright R.C., Fridman R. Differential regulation of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 expression in co-cultures of prostate cancer and stromal cells // Int. J. Cancer. – 2001. – Vol. 93. – P. 507-515.Dong Z., Nemeth J.A., Cher M.L., Palmer K.C., Bright R.C., Fridman R. Differential regulation of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 expression in co-cultures of prostate cancer and stromal cells // Int. J. Cancer. – 2001. – Vol. 93. – P. 507-515.Dutta J., Fan Y., Gupta N., Fan G. Gelinas C Current insights into the regulation of programmed cell death by NF NF-kappaB // Oncogene. – 2006. – Vol. 25. – P. 6800-6816.Dutta J., Fan Y., Gupta N., Fan G. Gelinas C Current insights into the regulation of programmed cell death by NF NF-kappaB // Oncogene. – 2006. – Vol. 25. – P. 6800-6816.Estrov Z., Shishodia S., Faderl S., Harris D., Van Q., Kantarjian H.M., Talpaz M., Aggarwal B.B. Resveratrol blocks interleukin-1beta-induced activation of the nuclear transcription factor NF- kappaB, inhibits proliferation, causes S-phase arrest, and induces apopto-sis of acute myeloid leukemia cells // Blood. – 2003. – Vol. 102. – P. 987-995.Estrov Z., Shishodia S., Faderl S., Harris D., Van Q., Kantarjian H.M., Talpaz M., Aggarwal B.B. Resveratrol blocks interleukin-1beta-induced activation of the nuclear transcription factor NF- kappaB, inhibits proliferation, causes S-phase arrest, and induces apopto-sis of acute myeloid leukemia cells // Blood. – 2003. – Vol. 102. – P. 987-995.Fan S., Gao M., Meng Q., Laterra J.J., Symons M.H., Coniglio S., Pestell R.G., Goldberg I.D., Rosen E.M. Role of NF-kappaB signaling in hepatocyte growth factor/scatter factor-mediated cell protection // Oncogene.– 2005. – Vol. 24. – P. 1749-1766.Fan S., Gao M., Meng Q., Laterra J.J., Symons M.H., Coniglio S., Pestell R.G., Goldberg I.D., Rosen E.M. Role of NF-kappaB signaling in hepatocyte growth factor/scatter factor-mediated cell protection // Oncogene.– 2005. – Vol. 24. – P. 1749-1766.Ghosh S., Baltimore D. Activation in vitro of NF-κB by phosphorylation of its inhibitor IκB // Nature. – 1990. – Vol. 344. – №6267. – P. 678-682.Ghosh S., Baltimore D. Activation in vitro of NF-κB by phosphorylation of its inhibitor IκB // Nature. – 1990. – Vol. 344. – №6267. – P. 678-682.Giri D.K., Aggarwal B.B. Constitutive activation of NF-kappaB causes resistance to apoptosis in human cutaneous T cell lymphoma HuT-78 cells. Autocrine role of tumor necrosis factor and reactive oxygen intermediates // J. Biol. Chem. – 1998. – Vol. 273 – P. 14008-14014.Giri D.K., Aggarwal B.B. Constitutive activation of NF-kappaB causes resistance to apoptosis in human cutaneous T cell lymphoma HuT-78 cells. Autocrine role of tumor necrosis factor and reactive oxygen intermediates // J. Biol. Chem. – 1998. – Vol. 273 – P. 14008-14014.Ho L., Davis R.E., Conne B., Chappuis R., Berczy M., Mhawech P., Staudt L.M., Schwaller J. MALT1 and the API2-MALT1 fusion act between CD40 and IKK and confer NF-kappa B-dependent proliferative advantage and resistance against FAS-induced cell death in B cells // Blood. – 2005. – Vol. 105. – №10. – P. 2891-2899.Ho L., Davis R.E., Conne B., Chappuis R., Berczy M., Mhawech P., Staudt L.M., Schwaller J. MALT1 and the API2-MALT1 fusion act between CD40 and IKK and confer NF-kappa B-dependent proliferative advantage and resistance against FAS-induced cell death in B cells // Blood. – 2005. – Vol. 105. – №10. – P. 2891-2899.Isaiah G., SchauerJing Z., Zhen X., Xiaoqing G., Imelda M-U., Anil K.S., Peng H., and Jinsong L.. Interleukin-1β Promotes Ovarian Tumorigenesis through a p53/NF-κB-Mediated Inflammatory Response in Stromal Fibroblasts // Neoplasia. – 2013. – Vol. 15. – №4. – P. 409-420.Isaiah G., SchauerJing Z., Zhen X., Xiaoqing G., Imelda M-U., Anil K.S., Peng H., and Jinsong L.. Interleukin-1β Promotes Ovarian Tumorigenesis through a p53/NF-κB-Mediated Inflammatory Response in Stromal Fibroblasts // Neoplasia. – 2013. – Vol. 15. – №4. – P. 409-420.Jacobs M.D., Harrison S.C. Structure of an IκBα/ NF-κB complex // Cell. – 1998. – Vol. 95. – №6. – P. 749-758.Jacobs M.D., Harrison S.C. Structure of an IκBα/ NF-κB complex // Cell. – 1998. – Vol. 95. – №6. – P. 749-758.Jagetia G.C., Aggarwal B.B. "Spicing up" of the immune system by curcumin // J. Clin. Immunol. – 2007. – Vol. 27. – P. 19-35.Jagetia G.C., Aggarwal B.B. "Spicing up" of the immune system by curcumin // J. Clin. Immunol. – 2007. – Vol. 27. – P. 19-35.Kalgutkar A.S., Zhao Z. Discovery and design of selective cyclooxygenase-2 inhibitors as non- ulcerogenic, anti-inflammatory drugs with potential utility as anti-cancer agents //Curr. Drug Targets. – 2001. – Vol. 2. – P. 79-106.Kalgutkar A.S., Zhao Z. Discovery and design of selective cyclooxygenase-2 inhibitors as non- ulcerogenic, anti-inflammatory drugs with potential utility as anti-cancer agents //Curr. Drug Targets. – 2001. – Vol. 2. – P. 79-106.Karin M., Lin A. NF-kappaB at the crossroads of life and death //Nat.Immunol.– 2002. – Vol. 3. – №3. – P. 221-227.Karin M., Lin A. NF-kappaB at the crossroads of life and death //Nat.Immunol.– 2002. – Vol. 3. – №3. – P. 221-227.Klotz T., Bloch W., Jacobs G., Niggemann S., Engelmann U., Addicks K. Immunolocalization of inducible and constitutive nitric oxide synthases in human bladder cancer // Urology. – 1999. – Vol. 54. – P. 416-419.Klotz T., Bloch W., Jacobs G., Niggemann S., Engelmann U., Addicks K. Immunolocalization of inducible and constitutive nitric oxide synthases in human bladder cancer // Urology. – 1999. – Vol. 54. – P. 416-419.Korkaya H., Paulson A., Iovino F., Wicha M.S.: HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion // Oncogene. – 2008. – Vol. 27. – P. 6120-6130.Korkaya H., Paulson A., Iovino F., Wicha M.S.: HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion // Oncogene. – 2008. – Vol. 27. – P. 6120-6130.Kouroukis C.T., Baldassarre F.G., Haynes A.E., Imrie K., Reece D.E., Cheung M.C. Bortezomib in Multiple Myeloma: A Practice Guideline // Clin. Oncol. (R. Coll. Radiol). – 2013. – Vol. 13. – P. 463-469.Kouroukis C.T., Baldassarre F.G., Haynes A.E., Imrie K., Reece D.E., Cheung M.C. Bortezomib in Multiple Myeloma: A Practice Guideline // Clin. Oncol. (R. Coll. Radiol). – 2013. – Vol. 13. – P. 463-469.Kwon O., Kim K., He L., Jung M., Jeong S., Ahn J.,Kim B. Complex formation of p65/RelA with nuclear Akt1 for enhanced transcriptional activation of NF-kappaB // Biochem. Biophys Res. Commun. – 2008. – Vol. 365.– P. 771-776.Kwon O., Kim K., He L., Jung M., Jeong S., Ahn J.,Kim B. Complex formation of p65/RelA with nuclear Akt1 for enhanced transcriptional activation of NF-kappaB // Biochem. Biophys Res. Commun. – 2008. – Vol. 365.– P. 771-776.Lee C.H., Jeon Y.T., Kim S.H., Song Y.S. NF-kappaB as a potential molecular target for cancer therapy //Biofactors. – 2007. – Vol. 29. – №1. – P. 19-35.Lee C.H., Jeon Y.T., Kim S.H., Song Y.S. NF-kappaB as a potential molecular target for cancer therapy //Biofactors. – 2007. – Vol. 29. – №1. – P. 19-35.Lenz G., Davis R.E., Ngo V.N., Lam L., George T.C., Wright G.W., Dave S.S., Zhao H., Xu W., Rosenwald A., Ott G., Muller-Hermelink H.K., Gascoyne R.D., Connors J.M., Rimsza L.M., Campo E., Jaffe E.S., Delabie J., Smeland E.B., Fisher R.I., Chan W.C., Staudt L.M. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma // Science. – 2008. – Vol. 319. – P. 1676-1679.Lenz G., Davis R.E., Ngo V.N., Lam L., George T.C., Wright G.W., Dave S.S., Zhao H., Xu W., Rosenwald A., Ott G., Muller-Hermelink H.K., Gascoyne R.D., Connors J.M., Rimsza L.M., Campo E., Jaffe E.S., Delabie J., Smeland E.B., Fisher R.I., Chan W.C., Staudt L.M. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma // Science. – 2008. – Vol. 319. – P. 1676-1679.Li Q., Verma I.M. NF-κB regulation in the immune system // Nat .Rev.Immunol. – 2002. – Vol. 2. – P. 331-367.Li Q., Verma I.M. NF-κB regulation in the immune system // Nat .Rev.Immunol. – 2002. – Vol. 2. – P. 331-367.Luo J.L., Kamata H., Karin M. IKK/NF-kappaB signaling: balancing life and death--a new approach to cancer therapy // J.Clin. Invest. – 2005. – Vol. 115. – P. 2625-2632.Luo J.L., Kamata H., Karin M. IKK/NF-kappaB signaling: balancing life and death--a new approach to cancer therapy // J.Clin. Invest. – 2005. – Vol. 115. – P. 2625-2632.Mabuchi S., Ohmichi M., Nishio Y., Hayasaka T., Kimura A., Ohta T., Saito M., Kawagoe J., Takahashi K., Yada-Hashimoto N., Sakata M., Motoyama T., Kurachi H., Tasaka K., Murata Y. Inhibition of NFkappaB increases the efficacy of cisplatin in in vitro and in vivo ovarian cancer models // J. Biol. Chem. – 2004. – Vol. 279. – №22. – P. 23477-23485.Mabuchi S., Ohmichi M., Nishio Y., Hayasaka T., Kimura A., Ohta T., Saito M., Kawagoe J., Takahashi K., Yada-Hashimoto N., Sakata M., Motoyama T., Kurachi H., Tasaka K., Murata Y. Inhibition of NFkappaB increases the efficacy of cisplatin in in vitro and in vivo ovarian cancer models // J. Biol. Chem. – 2004. – Vol. 279. – №22. – P. 23477-23485.Merkhofer E.C., Cogswell P., Baldwin A.S.: Her2 activates NF-kappa B and induces invasion through the canonical pathway involving IKK alpha // Oncogene. – 2010. – Vol. 29. – P. 1238-1248.Merkhofer E.C., Cogswell P., Baldwin A.S.: Her2 activates NF-kappa B and induces invasion through the canonical pathway involving IKK alpha // Oncogene. – 2010. – Vol. 29. – P. 1238-1248.Mimeault M., Batra S.K. Animal models relevant to human prostate carcinogenesis underlining the critical implication of prostatic stem/progenitor cells // Biochim.Biophys.Acta.– 2011. – Vol. 1816. – №1. – P. 25-37.Mimeault M., Batra S.K. Animal models relevant to human prostate carcinogenesis underlining the critical implication of prostatic stem/progenitor cells // Biochim.Biophys.Acta.– 2011. – Vol. 1816. – №1. – P. 25-37.Nakshatri H., Goulet R.J. Jr. NF-kappaB and breast cancer // Curr.Probl. Cancer.– 2002. – Vol. 26. – P. 282-309.Nakshatri H., Goulet R.J. Jr. NF-kappaB and breast cancer // Curr.Probl. Cancer.– 2002. – Vol. 26. – P. 282-309.Napetschnig J., Wu H. Molecular Basis of NF-κB Signaling // Annual. Review of Biophysics.– 2013. – Vol. 42. – P. 443-468.Napetschnig J., Wu H. Molecular Basis of NF-κB Signaling // Annual. Review of Biophysics.– 2013. – Vol. 42. – P. 443-468.Nguyen L.V., Vanner R., Dirks P., Eaves C.J. Cancer stem cells: an evolving concept // Nat. Rev. Cancer. – 2012. – Vol. 12. – №2. – P. 133-143.Nguyen L.V., Vanner R., Dirks P., Eaves C.J. Cancer stem cells: an evolving concept // Nat. Rev. Cancer. – 2012. – Vol. 12. – №2. – P. 133-143.Nikolopoulos S.N., Blaikie P., Yoshioka T., Guo W., Giancotti F.G. Integrin beta4 signaling promotes tumor angiogenesis // Cancer Cell.– 2004. – Vol. 6. – P. 471-483.Nikolopoulos S.N., Blaikie P., Yoshioka T., Guo W., Giancotti F.G. Integrin beta4 signaling promotes tumor angiogenesis // Cancer Cell.– 2004. – Vol. 6. – P. 471-483.Noguchi Y., Makino T., Yoshikawa T., Nomura K., Fukuzawa K., Matsumoto A., Yamada T. The possible role of TNF-alpha and IL-2 in inducing tumor-associated metabolic alterations // Surg. Today. – 1996. – Vol. 26. – P.36-41.Noguchi Y., Makino T., Yoshikawa T., Nomura K., Fukuzawa K., Matsumoto A., Yamada T. The possible role of TNF-alpha and IL-2 in inducing tumor-associated metabolic alterations // Surg. Today. – 1996. – Vol. 26. – P.36-41.Peng Y., Power M., Li B., Lin T. Inhibition of IKK down-regulates antigen + Ig E-induced TNF production by mast cells: a role for the IKK-IkappaB-NF-kappaB pathway in IgE-dependent mast cell activation // J. Leukoc. Biol.– 2005. – Vol. 77. – P. 975-983.Peng Y., Power M., Li B., Lin T. Inhibition of IKK down-regulates antigen + Ig E-induced TNF production by mast cells: a role for the IKK-IkappaB-NF-kappaB pathway in IgE-dependent mast cell activation // J. Leukoc. Biol.– 2005. – Vol. 77. – P. 975-983.Pianetti S., Arsura M., Romieu-Mourez R., Cof-fey R.J., Sonenshein G.E. Her-2/neu overexpression induces NF-kappaB via a PI3-kinase/Akt pathway involving calpain-mediated degradation of IkappaB-alpha that can be inhibited by the tumor suppressor PTEN // Oncogene. – 2001. – Vol. 20. – P. 1287-1299.Pianetti S., Arsura M., Romieu-Mourez R., Cof-fey R.J., Sonenshein G.E. Her-2/neu overexpression induces NF-kappaB via a PI3-kinase/Akt pathway involving calpain-mediated degradation of IkappaB-alpha that can be inhibited by the tumor suppressor PTEN // Oncogene. – 2001. – Vol. 20. – P. 1287-1299.Rajasekhar V.K., Studer L., Gerald W., Socci N.D., Scher H.I. Tumour-initiating stem-like cells in human prostate cancer exhibit increased NF-κB signaling // Nat.Commun.– 2011. – Vol. 2. – P. 162.Rajasekhar V.K., Studer L., Gerald W., Socci N.D., Scher H.I. Tumour-initiating stem-like cells in human prostate cancer exhibit increased NF-κB signaling // Nat.Commun.– 2011. – Vol. 2. – P. 162.Robert C. Bast Jr., Bryan Hennessy, and Gor-don B. Mills The biology of ovarian cancer: new opportunities for translation // Nat. Rev. Cancer. – 2009. – Vol. 9. – №6. – P. 415.Robert C. Bast Jr., Bryan Hennessy, and Gor-don B. Mills The biology of ovarian cancer: new opportunities for translation // Nat. Rev. Cancer. – 2009. – Vol. 9. – №6. – P. 415.Samanta A.K., Huang H.J., Bast R.C. Jr., Liao W.S. Overexpression of MEKK3 confers resistance to apoptosis through activation of NFkappaB // J. Biol. Chem. – 2004. – Vol. 279. – №9. – P. 7576-7583.Samanta A.K., Huang H.J., Bast R.C. Jr., Liao W.S. Overexpression of MEKK3 confers resistance to apoptosis through activation of NFkappaB // J. Biol. Chem. – 2004. – Vol. 279. – №9. – P. 7576-7583.Sethi G., Ahn K.S., Xia D., Kurie J.M., Aggarwal B.B. Targeted deletion of MKK4 gene potentiates TNF-induced apoptosis through the down-regulation of NF-kappa B activation and NF-kappa B-regulated antiapoptotic gene products // J.Immunol. – 2007. – Vol. 179. – P. 1926-1933.Sethi G., Ahn K.S., Xia D., Kurie J.M., Aggarwal B.B. Targeted deletion of MKK4 gene potentiates TNF-induced apoptosis through the down-regulation of NF-kappa B activation and NF-kappa B-regulated antiapoptotic gene products // J.Immunol. – 2007. – Vol. 179. – P. 1926-1933.Sinn D.I., Lee S.T., Chu K., Jung K.H., et al.Roh J.K. Proteasomal inhibition in intracerebral hemorrhage: neuroprotective and anti-inflammatory effects of bortezomib //Neuro sci. Res.– 2007. – Vol. 58. – P. 12-18.Sinn D.I., Lee S.T., Chu K., Jung K.H., et al.Roh J.K. Proteasomal inhibition in intracerebral hemorrhage: neuroprotective and anti-inflammatory effects of bortezomib //Neuro sci. Res.– 2007. – Vol. 58. – P. 12-18.Sorriento D., Illario M., Finelli R., Iaccarino G. To NFκB or not to NFκB: The Dilemma on How to Inhibit a Cancer Cell Fate Regulator // Transl.Med.UniSa. – 2012. – Vol. 4. – P. 73-85.Sorriento D., Illario M., Finelli R., Iaccarino G. To NFκB or not to NFκB: The Dilemma on How to Inhibit a Cancer Cell Fate Regulator // Transl.Med.UniSa. – 2012. – Vol. 4. – P. 73-85.Suh J., Payvandi F., Edelstein L.C., Amenta P.S., Zong W.X., Geґlinas C., Rabson A.B. Mechanisms of constitutive NF-kappaB activation in human prostate cancer cells // Prostate. – 2002. – Vol. 52. – P. 183-200.Suh J., Payvandi F., Edelstein L.C., Amenta P.S., Zong W.X., Geґlinas C., Rabson A.B. Mechanisms of constitutive NF-kappaB activation in human prostate cancer cells // Prostate. – 2002. – Vol. 52. – P. 183-200.Suh J., Rabson A.B. NF-kappaB activation in human prostate cancer: important mediator or epiphenomenon? // J. Cell Biochem. – 2004. – Vol. 91. – №1. – P. 100-117.Suh J., Rabson A.B. NF-kappaB activation in human prostate cancer: important mediator or epiphenomenon? // J. Cell Biochem. – 2004. – Vol. 91. – №1. – P. 100-117.Wilson W. III, Baldwin A.S. Maintenance of constitutive IkappaB kinase activity by glycogen syn-thase kinase-3alpha/beta in pancreatic cancer // Cancer Res. – 2008. – Vol. 68. – P. 8156-8163.Wilson W. III, Baldwin A.S. Maintenance of constitutive IkappaB kinase activity by glycogen syn-thase kinase-3alpha/beta in pancreatic cancer // Cancer Res. – 2008. – Vol. 68. – P. 8156-8163.Zhou Y., Eppenberger-Castori S., Eppenberger U., Benz C.C. The NFkappaB pathway and endocrine-resistant breast cancer // Endocr.Relat. Cancer. – 2005. – Vol. 12. – №1. – P. 37-46.Zhou Y., Eppenberger-Castori S., Eppenberger U., Benz C.C. The NFkappaB pathway and endocrine-resistant breast cancer // Endocr.Relat. Cancer. – 2005. – Vol. 12. – №1. – P. 37-46.

The authors declare that there are no conflicts of interest present.