Antitumour and antiangiogenic effects of IDN 5390, a novel C-seco taxane, in a paclitaxel-resistant human ovarian tumour xenograft

Our results indicate that in the INT.ACP/PTX tumour cells the resistance to PTX was mediated by expression of Pgp, because tumour cells displayed an increased expression of Pgp protein compared to the parental cell line A2780/DDP

G Petrangolini

2004

Scholarcy highlights

  • In recent years, many preclinical studies have indicated the possibility of using cytotoxic drugs as antiangiogenic agents for the antitumour therapy
  • The Pgp expression levels were investigated by FACS analysis in the parental A2780 and in its variant cell lines
  • Pgp was expressed at low level in A2780 and A2780/DDP cells, whereas an increased expression was found in INT.ACP/PTX cells
  • An increased Pgp level was found in A2780/DDP cells after exposure to taxanes, whereas no significant modulation was observed in A2780 and INT.ACP/PTX cells
  • Our results indicate that in the INT.ACP/PTX tumour cells the resistance to PTX was mediated by expression of Pgp, because tumour cells displayed an increased expression of Pgp protein compared to the parental cell line A2780/DDP
  • The high susceptibility of A2780/ DDP cells to acquire an MDR phenotype was supported by the increased expression of Pgp observed after treatment with taxanes in such cells
  • The effects of IDN 5390 on tumour angiogenesis in vivo are consistent with its ability to inhibit endothelial cell motility as well as to downregulate the expression of angiogenic growth factors

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