약학회지 (YAKHAK HOEJI)

  • 제47권3호
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  • Pages.159-166
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  • 2003
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  • 0377-9556(pISSN)
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  • 2383-9457(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

오가피로부터 분리된 조다당 분획물의 면역자극활성 및 Cisplatin과의 병용에 의한 항암 상승작용의 유도

Immunostimulation Activity of the Crude Polysaccharides Fractionated from Eleutherococcus senticosus, and its Application to Prevent of Tumors by Combination Therapy with Cisplatin

  • 발행 : 2003.06.01
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초록

In order to study the clinical usefulness of crude polysaccharides fractionated from Eleutherococcus senticosus, EN-3, in eliminating tumors, we have investigated the effect of combination therapy on the murine tumor metastasis and growth models. In experimental metastasis of colon26-M3.1 cells, prophylactic intravenous (i.v.) administration of EN-3 (0.5, 5, and 50 $\mu\textrm{g}$/mouse) inhibited tumor metastasis compared with tumor control group in 33.6, 66.8, and 81.8％ respectively. The administration of EN-3 (50 $\mu\textrm{g}$/mouse) also exhibited a 66.1％ therapeutic effect on lung tumor metastasis. Although EN-3 induced no toxic effect on both tumor cell and normal splenocyte in the concentration below 100 $\mu\textrm{g}$/mι in in vitro, it induced significant proliferating activity on normal splenocyte in the concentration-dependent manner. In an analysis of NK-cell activity, i.v. administration of EN-3 (4∼100 $\mu\textrm{g}$/mouse) significantly augmented NK cytotoxicity to YAC-1 tumor cells. The combination treatments of cisplatin (10 $\mu\textrm{g}$) and EN-3 (5 $\mu\textrm{g}$) induced synergistic effect on the inhibition of tumor metastasis in experimental tumor metastasis model produced by colon26-M3.1 cells. In addition, the combination treatments also exhibited prolongation of lifespan in S∼180 tumor bearing mouse for over the 60 days. Even though cisplatin (2.5 $\mu\textrm{g}$/mι) exhibited cytotoxicity to tumor cells and inhibited tumor growth over 95％ in in vitro, combination treatment with EN-3 (20 $\mu\textrm{g}$/mι) was induced splenocyte proliferation and produced cytokines, such as TNF-$\alpha$, IL-1 and IL-12, from the macrophages. These results suggested that EN-3 stimulate immune system non-specifically and apply to the biological response modifiers (BRM) in chemo-immunotherapy for tumor prevention.

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참고문헌

  1. Immunopharm v.30 The inhibitory effect of preoperative immunochemotherapy on the lymph node metastasis of murine MM48 tumor Kudo, C.;Saito, M.;Yoshida, T. https://doi.org/10.1016/0162-3109(95)00015-L
  2. Int. J. Immunopharmacol. v.22 Synergistic anti-tumor activity of a novel immunomodulator, BCH-1393, in combination with cyclophosphamide Kadhim, S.;Penney, C.;Lagraoui, M.;heibein, J.;Attardo, G.;Zacharie, B.;Connolly, T.;Gagnon, L. https://doi.org/10.1016/S0192-0561(00)00028-X
  3. Cancer. Chemother. Rep. v.55 Acute toxicologic and pathologic effects of cis-diaminedichloroplatinum (NSC-119875) in the male rat Kociba, R. J.;Sleight, S. D.
  4. Nature v.205 Inhibition of cell division in Escherichia coli by electrolysis products from a platinum electrode Rosenberg, B.;Van-Camp, L.;Krigas, T. L. https://doi.org/10.1038/205698a0
  5. J. Biol. Chem. v.242 The inhibition of growth or cell division in escherichia coli by different ionic species of platinum(IV) complexes Rosenberg, B.;Van-Camp, L.;Grimley, E. B.;Thomson, A. J.
  6. Chem. Biol. Interact. v.5 New platinum complexes with antitumor activity Connors, T. A.;Johns, M.;Ross, W. C. J. https://doi.org/10.1016/0009-2797(72)90078-6
  7. Cancer Chemother. Rep. v.54 Inhibition of dunning ascitic leukemia and Walker 256 carcinosarcoma with cis-diaminedichloroplatinum(NSC-119875) Kociba, R. J.;Sleight, S. D.;Rosenberg, B.
  8. Toxicol. Appl. Pharmacol. v.38 The nephrotic effects of cis-diaminedichloroplatinum (Ⅱ) (NSC-119875) in male F-344 rats Ward, J. M.;Fauve, K. A. https://doi.org/10.1016/0041-008X(76)90185-X
  9. Immunopharm. v.29 Curative treatments of murine colon26 solid tumors by immunochemotherapy with G-CSF and OK-432 Kudo, C.;Saito, M.;Yoshida, T. https://doi.org/10.1016/0162-3109(95)00060-7
  10. Recent Advances in the Pharmacology of Kampo Medicine Kawamura, H.;Takemoto, N.;Maruyama, H.;Komatsu, Y.;Aburada, M.;Hosoya, E.
  11. Recent advances in the Pharmacology of Kampo Medicine Takemoto, N.;Naruyama, H.;Kawamura, H.;Komatsu, Y.;Aburada, M.;Hosoya, E.;Yamada, H.;Kiyohara, H.;Cyong, J. C.
  12. J. Ethnopharmacol. v.72 Eleutherococcus senticosus Maxim. (Araliaceae) as an adaptogen: a closer look Davydov, M.;Krikorian, A. D. https://doi.org/10.1016/S0378-8741(00)00181-1
  13. J. Ethnopharmacol. v.79 Effect of Acanthopanax senticosus stem on mast cell-dependent anaphylaxis Yi, J. M.;Hong, S. H.;Kim, J. H.;Kim, H. K.;Song, H. J.;Kim, H. M. https://doi.org/10.1016/S0378-8741(01)00403-2
  14. Phytother. Res. v.14 Antioxidant and hepatoprotective effects of Acathopanax senticosus Lin, C. C.;Huang, P. C. https://doi.org/10.1002/1099-1573(200011)14:7<489::AID-PTR656>3.0.CO;2-G
  15. J. Pharm. Sci. v.73 Cytotoxic effects of E. senticosus aqueous extract against L1210 leukemia cells Hacker, B.;Medon, P. https://doi.org/10.1002/jps.2600730235
  16. Chinese J. Cancer. v.3 Antitumor and immunological activities of Acanthopanax senticosus (Rupr. et Maxim) Harms polysaccharides Cheng, X. J.;Li, P. Z.;Sheng, X. H.;Li, B. J.;Zhu, C. L.
  17. Phytother. Res. v.15 The synthesis of Rantes, G-CSF, IL-4, IL-5, IL-6, IL-12 and IL-13 in human whole-blood cultures is modulated by an extract from Eleutherococcus senticosus L. roots Schmolz, M. W.;Sacher, F.;Aicher, B. https://doi.org/10.1002/ptr.746
  18. Arzneimittelforschung v.51 Immunopharmacological in vitro effects of Eleutherococcus senticosus extracts Steinmann, G. G.;Esperester, A.;Joller, P.
  19. Arzneimittelforschung v.37 Flow-cytometric studies with Eleutherococcus senticosus extract as an immunomodulatory agent Bohn, B.;Nebe, C. T.;Birr, C.
  20. Sov. Med. v.5 Immunomodulating action of an Eleuterococcus extract in oncologic patients Kupin, V. I.;Polevaia, E. B.;Sorokin, A. M.
  21. Acta. Physiol. Pharmacol. Bulg. v.13 Effect of Eleutherococcus extract on the radioprotective action of adeturone Minkova, M.;Pantev, T.
  22. Plant. Sci. v.160 Triiodobenzoic acid, an auxin polar transport inhibitor, suppresses somatic embryo formation and postembryonic shoot/root development in Eleutherococcus senticosus Choi, Y. E.;Katsumi, M.;Sano, H.
  23. Vopr. Onkol. v.13 Extract of Eleutherococcus senticosus maxim and the therapeutic activity of cyclophosphane, ethymidine, and benzo-TEPA Monakhov, B. V.
  24. Vopr. Onkol. v.11 Influence of the liquid extract from the roots of Eleutherococcus senticosus on the toxicity and antitumor activity of cyclophosphan Monokhov, B. V.
  25. J. Immunol. Meth. v.94 Use of MTT colorimetric assay to measure cell activation Gerlier, D.;Thomasset, N. https://doi.org/10.1016/0022-1759(86)90215-2
  26. Int. J. Immunopharm. v.20 Prophylactic effect of Korean mistletoe (Viscum album coloratum) extract on tumor metastasis is mediated by enhancement of NK cell activity Yoon, T.J.;Yoo, Y.C.;Kang, T. B.;Baek, Y. J.;Song, S. K.;Lee, K. H.;Azuma, I.;Kim, J. B. https://doi.org/10.1016/S0192-0561(98)00024-1
  27. Vaccine v.6 Induction of tumoricidal macrophages and production cytokines by synthetic muramyl dipeptides analogues Saiki, I.;Saito, S.;Fujita, C.;Ishida, H.;Iida, J.;Murata, J.;Hasegawa, A.;Azuma, I. https://doi.org/10.1016/0264-410X(88)90218-6
  28. Vaccine v.12 MDP-Lys(L18), a lipophilic derivative of muramyl dipeptide, inhibits the metastasis of haematogenous and non-haematogenous tumours in mice Yoo, Y. C.;Saiki, I.;Sato, K.;Azuma, I. https://doi.org/10.1016/0264-410X(94)90057-4
  29. Cancer Res. v.62 Apoptotic pancreatic tumor cells are superior to cell lysates in promoting cross-priming of cytotoxic T cells and activate NK and gammadelta T cells Schnurr, M.;Scholz, C.;Rothenfusser, S.;Galambos, P.;Dauer, M.;Robe, J.;Endres, S.;Eigler, A.
  30. Cancer Res. v.45 Macrophage and metastasis-a biological approach to cancer therapy: presidential address Fidler, I. J.