Antitumor effect on SN-38, active form of CPT-11, on human colorectal cancer cell line

The in vitro sensitivity testing for four human colorectal cancer cell lines to seven chemotherapeutic drugs including CPT-11, derivative of camptothecine, and its active form SN-38 were determined. MTT assay revealed that SN-38 was the most active for all four cell lines tested and its IC₅₀'s were very close to its clinically achievable plasma concentration. Relationship between exposure time and cytocidal effect of SN-38 was also investigated using MTT assay, topoisomerase-I (Topo-I) immunoblot analysis and DNA relaxation assay, showing that IC₅₀ value, Topo-I protein and Topo-I activity were decreased soon after the administration of SN-38 and reached the plateau level at 24 hours. We conclude that SN-38 is very potent for colorectal cancer and the optimal schedule of CPT-11 can be the more continuous form of administration capable of as long as 24 hours exposure of its active metabolite, SN-38.