Cisplatin and Oxaliplatin Cytotoxic Effects in Sensitive and Cisplatin-resistant Human Cervical Tumor Cells: Time and Mode of Application Dependency

• Published in: Anticancer research 2009-10, Vol.29 (10), p.3931-3937
• Main Authors: MARTELLI, Laura, RAGAZZI, Eugenio, DI MARIO, Francesco, BASATO, Marino, MARTELLI, Mario
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Biological and medical sciences; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - metabolism; Cell Line, Tumor; Cisplatin - administration & dosage; Cisplatin - pharmacokinetics; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Female; Humans; Medical sciences; Organoplatinum Compounds - administration & dosage; Organoplatinum Compounds - pharmacokinetics; Structure-Activity Relationship; Tumors; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - metabolism
• ISSN: 0250-7005; 1791-7530

Background: Time-dependence of cisplatin (CDDP) and oxaliplatin (L-OHP) cytotoxic effects in A431 and A431/Pt cells (sensitive and CDDP-resistant human cervical tumor cells) were investigated. Materials and Methods: The drug application modes were pulse (12.5, 25 or 50 μM up to 72 h) and pulse-plus-chase (50 μM for 2, 4 or 6h, followed by washing and 72 h-incubation in drug-free medium). Results: In the A431 cells, the pulse drug application showed time-effect curves with two plateaux; the inhibitory activity of CDDP was higher than that of L-OHP. The same growth-inhibition fraction was reached by L-OHP in a longer time than CDDP. In the A431/Pt cells, the curve shapes for both drugs were similar in both application modes and had the same general characteristics, noted in the parental cell line. CDDP appeared less active than L-OHP. Conclusion: Different cytotoxicity curves of Pt-drugs could be dictated by the presence of the bulky diaminocyclohexane (DACH) ligand, affecting the kinetics of Pt-DNA binding; mismatch repair (MSH2) protein is involved in the resistance.