Synergism from combinations of cisplatin with designed trans-platinums in the human ovarian tumour models
Fehmida Fasim
Discipline of Biomedical Sciences
Sydney Medical School
School of Medical Sciences
The University of Sydney
Cumberland Campus C42
75 East St , Lidcombe NSW 1825
AUSTRALIA
Abstract:
Combinations of cisplatin and its analogues with tumour active compounds such as paclitaxel and gemcitabine are currently used in the clinic or being investigated to overcome drug resistance leading to increased survival (1). In this study, synergism in activity from combinations of cisplatin with a number of newly synthesised trans-platinum compounds of structure {trans-Pt(L)2( R)2}; {trans-Pt(NH3)(L)(R)2} and {[trans-Pt(L)2[3-hydroxypyridine)2]} [where L= [imidazole(1,2-a)pyridine] and R = CH3COO} have been investigated, as applied to the human ovarian A2780, A2780cisR and A2780ZD0473R cancer cell lines with the aim of obtaining information on the effect of concentration and the sequence of administration on the synergism. Such information is considered to have clinical significance since synergism in activity from drug combination may provide a means of overcoming drug resistance and reducing the side effects. Dose-response curves have been generated and combination index (CI) values have been calculated to provide complimentary measures of synergism, additiveness and antagonism. The results showed that the binary combinations of cisplatin with transplatinums produce both sequence- and concentration-dependent synergism in all the three human ovarian cancer cell liners. The degree of synergism is found to be greater in a sequenced addition than the bolus, with the 0/4 h addition showing the strongest synergism.
Keywords: Synergism, transplatinums, drug resistance
