Augmented antitumour effects of combination therapy with TNP-470 and chemoimmunotherapy in mice

Anna Dabrowska-Iwanicka, Dominika Olszewska, Ahmad Jalili, Marcin Makowski, Tomasz Grzela, Maria Marczak, Grazyna Hoser, Adam Giermasz, Jakub Golab, Marek Jakóbisiak

Research output: Contribution to journalArticle

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Abstract

Purpose: To investigate antitumour efficacy of the combination of the antiangiogenic agent TNP-470 combined with chemoimmunotherapy in different tumour models in mice. Materials: B6D2F1 mice and BALB/c mice were inoculated in the footpad of the right hind limb with B16F10 melanoma cells or colon adenocarcinoma cells C-26, respectively. Subsequently, they received therapy consisting of TNP-470 and/or IL-12 and tumour growth was observed. In the melanoma model this therapy regimen was combined with cisplatin in a subtherapeutic dose. The antiangiogenic action of the tested agents was evaluated using tumour-induced angiogenesis assay in vivo. In order to analyse interactions between TNP-470 (or cisplatin) and IFN-γ on tumour cells in vitro, the following methods were used: MTT assay, Western blot analysis, and flow cytometry analysis. Results: Administration of the combined therapy with TNP-470 and IL-12 resulted in augmented antitumour activity in colon-26 and B16F10 melanoma models. Addition of cisplatin further enhanced efficacy of this combined therapy in the melanoma model. We showed that antitumour activity of this combined therapy is mediated by multiple mechanisms: not only is enhancement of the antiangiogenic activity mediated by TNP-470 and IL-12 but also by the synergistic cytostatic/cytotoxic action of IL-12-induced IFN-γ and TNP-470 or cisplatin on tumour cells. The experiments revealed that TNP-470 together with IFN-γ leads to the increased expression of p21 protein in cancer cells, which in turn may contribute to their cytostatic/cytotoxic action in vitro. Conclusion: Our experiments show a successful TNP-470-based combination therapy and suggest that the enhancement of the antitumour activity could be explained by a concomitant effect on both endothelial and tumour cell compartments.

Original languageEnglish (US)
Pages (from-to)433-442
Number of pages10
JournalJournal of Cancer Research and Clinical Oncology
Volume128
Issue number8
DOIs
StatePublished - 2002
Externally publishedYes

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Interleukin-12
Cisplatin
Melanoma
Neoplasms
Cytostatic Agents
Therapeutics
Colon
Angiogenesis Inhibitors
O-(chloroacetylcarbamoyl)fumagillol
Flow Cytometry
Adenocarcinoma
Extremities
Endothelial Cells
Western Blotting
Growth
Proteins
In Vitro Techniques

Keywords

  • Antiangiogenic agents
  • IL-12
  • Melanoma
  • Mice
  • TNP-470
  • Tumour therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Dabrowska-Iwanicka, A., Olszewska, D., Jalili, A., Makowski, M., Grzela, T., Marczak, M., ... Jakóbisiak, M. (2002). Augmented antitumour effects of combination therapy with TNP-470 and chemoimmunotherapy in mice. Journal of Cancer Research and Clinical Oncology, 128(8), 433-442. https://doi.org/10.1007/s00432-002-0356-z

Augmented antitumour effects of combination therapy with TNP-470 and chemoimmunotherapy in mice. / Dabrowska-Iwanicka, Anna; Olszewska, Dominika; Jalili, Ahmad; Makowski, Marcin; Grzela, Tomasz; Marczak, Maria; Hoser, Grazyna; Giermasz, Adam; Golab, Jakub; Jakóbisiak, Marek.

In: Journal of Cancer Research and Clinical Oncology, Vol. 128, No. 8, 2002, p. 433-442.

Research output: Contribution to journalArticle

Dabrowska-Iwanicka, A, Olszewska, D, Jalili, A, Makowski, M, Grzela, T, Marczak, M, Hoser, G, Giermasz, A, Golab, J & Jakóbisiak, M 2002, 'Augmented antitumour effects of combination therapy with TNP-470 and chemoimmunotherapy in mice', Journal of Cancer Research and Clinical Oncology, vol. 128, no. 8, pp. 433-442. https://doi.org/10.1007/s00432-002-0356-z
Dabrowska-Iwanicka, Anna ; Olszewska, Dominika ; Jalili, Ahmad ; Makowski, Marcin ; Grzela, Tomasz ; Marczak, Maria ; Hoser, Grazyna ; Giermasz, Adam ; Golab, Jakub ; Jakóbisiak, Marek. / Augmented antitumour effects of combination therapy with TNP-470 and chemoimmunotherapy in mice. In: Journal of Cancer Research and Clinical Oncology. 2002 ; Vol. 128, No. 8. pp. 433-442.
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AU - Grzela, Tomasz

AU - Marczak, Maria

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