Activity of lipoplatin in tumor and in normal cells in vitro.
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.
Arienti
Chiara
C
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, via P. Maroncelli 40, Meldola, Italy.
Tesei
Anna
A
Ravaioli
Alberto
A
Ratta
Marina
M
Carloni
Silvia
S
Mangianti
Serena
S
Ulivi
Paola
P
Nicoletti
Stefania
S
Amadori
Dino
D
Zoli
Wainer
W
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020128:Inhibitory Concentration 50
D000970:Antineoplastic Agents; C503131:lipoplatin; D002945:Cisplatin