SURAMIN INTERFERES WITH AUTO PARACRINE INSULIN-LIKE GROWTH-FACTOR I-CONTROLLED PROLIFERATIVE LOOP ON HUMAN LUNG-CANCER CELL-LINES/

Human non-small cell lung cancer (N-SCLC), a common malignancy general ly unmanageable by conventional cytotoxic chemotherapy, represents a m ajor world health burden. Suramin, a polyanionic drug which appears to interfere with growth-factor/receptor interaction, has recently been shown to be cytostatic for small cell lung cancer cells; it may also b e effective for N-SCLC. As insulin-like growth factor I (IGF-I) is a k nown progression agent for N-SCLC, we have examined the effects of sur amin on the 'IGF-I system' in a panel of human N-SCLC cell lines. Colo rimetric and thymidine incorporation assays were used to assess cell c hemosensitivity whereas a radio-receptor assay was employed to evaluat e IGF-I/receptor binding. Suramin reversibly reduced, in a concentrati on- and time-dependent manner, the growth of each N-SCLC cell line exa mined either cultured in serum-containing or serum-free medium. Furthe rmore, suramin caused a concentration-related inhibition of labeled IG F-I peptide specific binding on all cell lines studied. Suramin caused a significant reduction in the beta(max) values with only weak max va riations in the affinity constants (K-d). We hypothesize that suramin interference with IGF-I mitogenic activity is a pathway by which this drug produces its effect in vitro. These data indicate further studies on the mechanism of action and pharmacology of suramin in vivo are wa rranted.