RESULTS: In terms of IC(50) values, the cytotoxicity of LDM was 10 000-fold more potent than that of
mitomycin C (MMC) and
adriamycin (ADM) in human
hepatoma BEL-7402 cells and SMMC-7721 cells. LDM molecule consists of two moieties, an aproprotein (LDP) and an enediyne chromophore (LDC). In terms of IC(50) values, the potency of LDC was similar to LDM. However, LDP was 10(5)-fold less potent than LDM and LDC to
hepatoma cells. For mouse
hepatoma H22 cells, the IC(50) value of LDM was 0.025 nmol/L. Given by single
intravenous injection at doses of 0.1, 0.05 and 0.025 mg/kg, LDM markedly suppressed the growth of
hepatoma 22 in mice by 84.7%, 71.6% and 61.8%, respectively. The therapeutic indexes (TI) of LDM and MMC were 15 and 2.5, respectively. By 2 iv.
injections in two experiments, the growth inhibition rates by LDM at doses of 0.1, 0.05, 0.025, 0.00625 and 0.0125 mg/kg were 88.8-89.5%, 81.1-82.5%, 71.2-74.9%, 52.3-59.575%, and 33.3-48.3%, respectively. In comparison, MMC at doses of 5, 2.5, and 1.25 mg/kg inhibited
tumor growth by 69.7-73.6%, 54.0-56.5%, and 31.5-52.2%, respectively. Moreover, in human
hepatoma BEL-7402 xenografts, the growth inhibition rates by LDM at doses of 0.05 mg/kg X2 and 0.025 mg/kg X2 were 68.7% and 27.2%, respectively. However, MMC at the dose of 1.25 mg/kg X2 showed an inhibition rate of 34.5%. The inhibition rate of
tumor growth by LDM was higher than that by MMC at the tolerated dose.
CONCLUSION: