SURAMIN IS SYNERGISTIC WITH VINBLASTINE IN HUMAN COLONIC TUMOR-CELL LINES - EFFECT OF CELL-DENSITY AND TIMING OF DRUG-DELIVERY

Suramin is a multi-targeted antiproliferative drug developed for the t reatment of African trypanosomiasis but with potential efficacy for th e treatment of human cancer. Cell growth inhibition was determined in vitro for three human colonic tumor cell lines using three different d oses of suramin (50, 100 and 200 mu M). At the lower suramin concentra tion cell growth was stimulated relative to control cultures in all th ree cell lines. At the higher dose which is at the upper end of the to lerable dose in humans suramin reduced cell numbers by greater than 50 %. Inhibition of cellular proliferation was reduced relative to increa ses in cell plating density. Addition of vinblastine six and to a less er extent 72 hours post suramin (200 mu M) resulted in an inhibition o f cell growth and/or toxicity that exceeded that which occurred as a r esult of exposure to either suramin or vinblastine alone. To investiga te the possible mechanism by which suramin sensitizes cells to vinblas tine we determined the effect of suramin on expression of the multidru g resistance (mdr1) gene. A decrease in mdr1 mRNA was evident in one c olon tumor cell line and a slight decrease detected in a second line. The results establish that suramin is effective in controlling growth in colonic tumor cells and confirms that suramin activity is synergist ic with other chemotherapeutics. The effect of suramin on MDR is of po tential value that needs to be more thoroughly investigated particular ly in cancers such as the those of the colon that are often drug refra ctory.