THE EFFECT OF SN-38 ON CELL-PROLIFERATION AND ON PRODUCTION OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR AND ITS INHIBITOR IN HUMAN LUNG-CANCER CELL-LINES

The plasminogen activator system has been found to modulate neoplastic spread and angiogenesis in tumors. SN-38, a metabolite of CPT-11, whi ch is a camptothecin derivative has been shown to possess potent cytot oxicity in various kinds of human cancers. We investigated the effect of SN-38 on cancer cell proliferation and on production of urokinase-t ype plasminogen activator (u-PA) and its inhibitor (PAI-1) in human lu ng cancer cell lines, TKB-2 and TKB-30. SN-38 inhibited cell prolifera tion in a dose-dependent manner in both cell lines. u-PA and PAI-1 in culture supernatants were suppressed with SN-38, in association with t he decrease in viable cancer cells. Since a crucial balance between u- PA and PAI-1 is necessary for optimal invasiveness, the inhibitory eff ects of SN-38 on cell proliferation and on the plasminogen activator s ystem would be of advantage to the treatment of cancer.