Antitumour and antiangiogenic activities of [Pt(O,O'-acac)(γ-acac)(DMS)] in a xenograft model of human renal cell carcinoma

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Abstract

BACKGROUND AND PURPOSE It is thought that the mechanism of action of anticancer chemotherapeutic agents is mainly due to a direct inhibition of tumour cell proliferation. In tumour specimens, the endothelial cell proliferation rate increases, suggesting that the therapeutic effects of anticancer agents could also be attributed to inhibition of tumour angiogenesis. Hence, we investigated the potential effects of [Pt (O,O′-acac)(γ-acac)(DMS)] ([Pt(DMS)]), a new platinum drug for non-genomic targets, on human renal carcinoma and compared them with those of the well-established anticancer drug, cisplatin. EXPERIMENTAL APPROACH Tumour growth, tumour cell proliferation and microvessel density were investigated in a xenograft model of renal cell carcinoma, developed by injecting Caki-1 cells into BALB/c nude mice. The antiangiogenic potential of compounds was also investigated using HUVECs. KEY RESULTS Treatment of the Caki-1 cells with cisplatin or [Pt(DMS)] resulted in a dose-dependent inhibition of cell survival, but the cytotoxicity of [Pt(DMS)] was approximately fivefold greater than that of cisplatin. [Pt(DMS)] was much more effective than cisplatin at inhibiting tumour growth, proliferation and angiogenesis in vivo, as well as migration, tube formation and MMP1, MMP2 and MMP9 secretion of endothelial cells in vitro. Whereas, cisplatin exerted a greater cytotoxic effect on HUVECs, but did not affect tube formation or the migration of endothelial cells. In addition, treatment of the xenograft mice with [Pt(DMS)] decreased VEGF, MMP1 and MMP2 expressions in tumours. CONCLUSIONS AND IMPLICATIONS The antiangiogenic and antitumour activities of [Pt(DMS)] provide a solid starting point for its validation as a suitable candidate for further pharmacological testing.

Autore Pugliese

Tutti gli autori

  • Muscella A. , Vetrugno C. , Biagioni F. , Calabriso N. , Calierno M. T. , Fornai F. , De Pascali S. A. , Marsigliante S. , Fanizzi F. P.

Titolo volume/Rivista

BRITISH JOURNAL OF PHARMACOLOGY

Anno di pubblicazione

2016

ISSN

0007-1188

ISBN

Non Disponibile

Numero di citazioni Wos

Nessuna citazione

Ultimo Aggiornamento Citazioni

Non Disponibile

Numero di citazioni Scopus

3

Ultimo Aggiornamento Citazioni

28/04/2018

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile