Experiments on male C57Bl/6 mice with transplantable Lewis lung epidermoid carcinoma were performed to evaluate the effect of early or delayed administration of compound SNK-411 (2-isobutyl-4,6-dimethyl-5-hydroxypyrimidine) on tumor growth and animal survival. Intraperitoneal injection of SNK-411 in doses of 25 and 50 mg/kg on days 2–8 of tumor growth was followed by significant inhibition of tumor growth (by 1.8 and 2.2 times, respectively, in comparison with the untreated control). Administration of this compound on days 8–15 of tumor development had little effect on tumor growth. SNK-411 in doses of 25 and 50 mg/kg (both dosing regimens) significantly increased survival rate and lifespan of animals with tumors. The drugs for verification of this model (Fluorofur, 400 mg/kg; and doxorubicin hydrochloride, 4 mg/kg) were injected intraperitoneally on days 2–4 and 8–10 of tumor development. Administration of Fluorofur and doxorubicin hydrochloride at the late stage was accompanied by significant inhibition of tumor growth (by 1.6 and 1.4 times, respectively). The increase in the survival rate of animals receiving the cytostatic according to standard dosing regimens was less significant than in experiments with SNK-411.
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References
E. D. Goldberg, T. G. Razina, E. P. Zueva, E. N. Amosova, S. G. Krylova, and V. E. Goldberg, Plants in the complex therapy of tumors [in Russian], Moscow (2008), pp. 72–76.
N. A. Zhukova, I. V. Sorokina, T. G. Tolstikova, M. P. Dolgikh, and D. E. Semenov, Effect of Betulonic Acid and Its Derivatives on the Morphology of Kidneys in the Animals with Transplanted Lewis Lung Carcinoma at the Background of Polychemotherapy and without It. Chemistry for Sustainable Development, 18, No. 4, 403–408 (2010).
A. V. Lichtenstein, Cancer research: A hurdle race. Biochemistry (Mosc.), 79, No. 5, 385–390 (2014).
S. B. Seredin, C. V. Nikitin, L. P. Kovalenko, and A. D. Durnev, Patent RF No. 2518889. 5-Oxypyrimidine Derivative Possessing Antineoplastic Activity, Bull., No. 16 (June 10, 2014).
E. M. Treshchalina, O. S. Zhukova, G. K. Gerasimova, N. V. Andronova, and A. M. Garin, Manual of Preclinical Studies of New Drugs, Ed. A. N. Mironov [in Russian], Moscow (2012), pp. 642–656.
J. M. Fauci, F. Sabbatino, Y. Wang, A. I. Londono-Joshi, J. M. Straughn Jr, C. N. Landen, S. Ferrone, and D. J. Buchsbaum, Monoclonal antibody-based immunotherapy of ovarian cancer: targeting ovarian cancer cells with the B7-H3-specific mAb 376.96. Gynecol. Oncol., 132, No. 1, 203–210 (2014).
F. Ito and A. E. Chang, Cancer immunotherapy: current status and future directions. Surg. Oncol. Clin. N. Am., 22, No. 4, 765–783 (2013).
E. Jedrych, S. Flis, K. Sofinska, Z. Jastrzebski, M. Chudy, A. Dybko, and Z. Brzozka, Evaluation of cytotoxic effects of 5-fluorourcil on human carcinoma cells in microfluidic system. Sens. Actuators B Chem., 160, No. 1, 1544–1551 (2011).
Z. Li, L. Chen, and Z. Qin, Paradoxical roles of IL-4 in tumor immunity. Cell. Mol. Immunol., 6, No. 6, 415–422 (2009).
H. Roca, M. J. Craig, C. Ying, Z. S. Varsos, P. Czarnieski, A. S. Alva, J. Hernandez, D. Fuller, S. Daignault, P. N. Healy, and K. J. Pienta, IL-4 induces proliferation in prostate cancer PC3 cells under nutrient-depletion stress through the activation of the JNK-pathway and surviving up-regulation. J. Cell. Biochem., 113, No. 5, 1569–1580 (2012).
K. Taniguchi and M. Karin, IL-6 and related cytokines as the critical lynchpins between inflammation and cancer. Semin. Immunol., 26, No. 1, 54–74 (2014).
Z. C. Tucker, B.A. Laguna, E. Moon, and S. Singhal, Adjuvant immunotherapy for non-small cell lung cancer. Cancer Treat. Rev., 38, No. 6, 650–661 (2012).
Y. Yoshimoto, M. Kawada, D. Ikeda, and M. Ishizuka, Involvement of doxorubicin-induced Fas expression in the antitumor effect of doxorubicin on Lewis lung carcinoma in vivo. Int. Immunopharmacol., 5, No. 2, 281–288 (2005).
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 161, No. 1, pp. 114–118, January, 2016
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Kovakenko, L.P., Kuznetsova, O.S., Tallerova, A.V. et al. Effect of 2-Isobutyl-4,6-dimethyl-5-hydroxypyrimidine on the Growth of Lewis Lung Carcinoma and Survival of Mice. Bull Exp Biol Med 161, 99–103 (2016). https://doi.org/10.1007/s10517-016-3355-9
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DOI: https://doi.org/10.1007/s10517-016-3355-9