The effect of monotherapy and combined therapy with NSC-631570 (Ukrain) on growth of low- and high-metastasizing B16 melanoma in mice

Background. NSC-631570 (Ukrain) is a semisynthetic derivative of the Chelidonium majus alcaloids and the alkylans thiotepa. It exerts a selective cytotoxic effect on tumor cells in vitro and in vivo and shows the ability to modulate immunocyte functions. Purpose. The aim of our work was to carry out...

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Bibliographic Details
Published in:Journal of oncology pharmacy practice 2011-12, Vol.17 (4), p.339-349
Main Authors: Skivka, LM, Susak, YaM, Trompak, OO, Kudryavets, YuI, Bezdeneznikh, N, Semesiuk, N, Lykhova, O
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Berberine Alkaloids - administration & dosage
Cell Death - drug effects
Cell Death - physiology
Drug therapy
Female
Melanoma, Experimental - drug therapy
Melanoma, Experimental - pathology
Melanoma, Experimental - secondary
Metastasis
Mice
Mice, Inbred C57BL
Phenanthridines - administration & dosage
Random Allocation
Rodents
Skin cancer
Tumor Cells, Cultured
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Summary:Background. NSC-631570 (Ukrain) is a semisynthetic derivative of the Chelidonium majus alcaloids and the alkylans thiotepa. It exerts a selective cytotoxic effect on tumor cells in vitro and in vivo and shows the ability to modulate immunocyte functions. Purpose. The aim of our work was to carry out a comparative investigation of the effects of NSC-631570 alone or in combination with pathogen-associated molecules (PAM) on the growth of low- and high-metastasizing melanoma B16 in mice. Methods. NSC-631570 was administered intravenously and PAM intramuscularly to tumor-bearing mice seven times every third day, starting from the second day after the transplantation of tumor cells. The effect of monotherapy and combined therapy on tumor growth was evaluated by the indices of tumor growth inhibition in experimental animals. Cell cycle distribution of cancer cells was determined by flow cytometry. TAP1 and TAP2 expression was evaluated by RT-PCR. The metabolic activity of phagocytes was determined by NBT-test, phagocytosis was tested by flow cytometry, and arginase activity was estimated by colorimetric determination of urea. Results. Combined therapy and monotherapy with NSC-631570 resulted in significant inhibition of tumor growth in melanoma-bearing mice. Monotherapy with Ukrain was more effective in mice with high-metastasizing tumors. The therapeutic efficacy of NSC-631570 used in combination with PAM was more expressed in mice with low-metastasizing melanoma. Conclusion. The effectiveness of monotherapy and combined therapy with NSC-631570 in the treatment of melanoma B16 depends on the biological properties of the tumor and the immune state of the organism.
ISSN:1078-1552
1477-092X
DOI:10.1177/1078155210382470