IN-VITRO SCHEDULE-DEPENDENCY OF EO9 AND MILTEFOSINE IN COMPARISON TO STANDARD DRUGS IN COLON-CANCER CELLS

In vitro screening of new antitumor drugs is often limited to fast chemosensitivity assays. The potency of drugs is studied by measuring growth inhibition at the end of the assay after a fixed drug exposure time. In this study, the human colon cancer cell lines HT29 and SW620, were exposed to drugs for 1 h, 24 h (followed by culture in drug-free medium), 72 h and for 72 h with drug renewal every 24 h. Growth inhibition was evaluated at 48 and 72 h after initial drug addition, using the sulforhodamine B (SRB) assay. Chemosensitivity profiles of the investigational drugs EO9, a bioreductive alkylator, and the ether lipid miltefosine (HPC), were compared to those of drugs with different mechanisms of action: doxorubicin, cisplatin (DDP) and 5-fluorouracil. HPC displayed recovery from growth inhibition, in both cell lines, after drug exposures of 1 and 24 hours. DDP showed an increase for both cell lines (p < 0.05) of growth inhibition when drug was being refreshed every 24 h, compared to 72 h continuous drug exposure. Doxorubicin, 5-fluorouracil and EO9 were more potent in SW620 cells. These data suggest that more initial information can be obtained from drug screening assays, when both continuous and short-term drug exposures are studied, instead of one fixed drug exposure time, and indicates that daily renewal of drugs, may reveal possible drug stability and availability problems.