Cisplatin and oxaliplatin cytotoxic effects in sensitive and cisplatin-resistant human cervical tumor cells: time and mode of application dependency.

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 microM up to 72 h) and pulse-plus-chase (50 microM for 2, 4 or 6 h, 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.