Antitumour and antiangiogenic activities of [Pt(O,O'-acac)(γ-acac)(DMS)] in a xenograft model of human renal cell carcinoma
| Autor: | Muscella, A, Vetrugno, C, Biagioni, F, Calabriso, N, Calierno, Mt, Fornai, Francesco, De Pascali, Sa, Marsigliante, S, Fanizzi, F. p. |
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| Přispěvatelé: | Muscella, Antonella, Vetrugno, Carla, Biagioni, F, Calabriso, Nadia, Calierno, M. T, Fornai, F, DE PASCALI, SANDRA ANGELICA, Marsigliante, Santo, Fanizzi, Francesco Paolo |
| Rok vydání: | 2015 |
| Předmět: |
RANDOMIZED PHASE-3 TRIAL
BREAST-CANCER CELLS TUMOR ANGIOGENESIS TESTICULAR CANCER PLATINUM(II) COMPLEXES ENDOTHELIAL-CELL IN-VIVO GROWTH CISPLATIN PATHWAY Organoplatinum Compounds Cell Survival Mice Nude Angiogenesis Inhibitors Antineoplastic Agents renal cell carcinoma VEGF xenograft [Pt(O O′-acac)(γ-acac)(DMS)] MMPs matrix metalloprotease Mice Structure-Activity Relationship Tumor Cells Cultured Animals Humans Carcinoma Renal Cell Cell Proliferation Mice Inbred BALB C Dose-Response Relationship Drug Neoplasms Experimental Xenograft Model Antitumor Assays Research Papers Kidney Neoplasms |
| Zdroj: | British journal of pharmacology. 173(17) |
| ISSN: | 1476-5381 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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