Activity of lipoplatin in tumor and in normal cells in vitro

Chiara Arienti, Anna Tesei, Alberto Ravaioli, Marina Ratta, Silvia Carloni, Serena Mangianti, Paola Ulivi, Stefania Nicoletti, Dino Amadori, Wainer Zoli

Research output: Contribution to journalArticlepeer-review

Abstract

Lipoplatin is a novel liposomal cisplatin formulation with reduced adverse side effects compared with its parental compound, cisplatin. The aims of this preclinical study were to compare lipoplatin and cisplatin cytotoxicity in vitro in established cell lines derived from non-small cell lung cancer, renal cell carcinoma, and in normal hematopoietic cell precursors, and to identify biological markers associated with sensitivity and resistance. Our results showed a superior cytotoxicity in all tumor cell models and a much lower toxicity in normal cells for lipoplatin compared with cisplatin, suggesting a higher therapeutic index for the liposomal compound. Moreover, RT-PCR analysis of molecular markers known to be related to cisplatin resistance showed a direct correlation between cisplatin and lipoplatin resistance and ERCC1 and LRP expression. In conclusion, lipoplatin showed a higher antitumor activity in both tumor histotypes investigated and was found to be safer than the parent compound, cisplatin. Moreover, ERCC1 and LRP expression levels would seem to be valid predictors of sensitivity or resistance to these drugs.

Original languageEnglish
Pages (from-to)983-990
Number of pages8
JournalAnti-Cancer Drugs
Volume19
Issue number10
DOIs
Publication statusPublished - Nov 2008

Keywords

  • ERCC1
  • Lipoplatin
  • LRP
  • MDR-1
  • Non-small cell lung cancer
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research
  • Oncology

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