Studies Of The Potent Cytotoxicity Of Lidamycin On Multidrug Resistant Cancer Cells And Novel Antitumor Biochemical Modulators

Lidamycin (LDM), a member of macromolecular antibiotic with an enediyne chromophore, displays extremely potent cytotoxisity against tumor cells. Previous studies demonstrated that it could directly cleave DNA strands with preference of nucleotide sequence, and indicated that it was potentially valuable to be used clinically. As well known, one of the greatest obstacles of tumor chemotherapy focused on the multidrug resistant (MDR) cancer cells. The anti-MDR cancer cell activity of LDM was reported in the first part of this thesis.Biochemical modulators were a kind of compounds, which targeted a special process or molecules in biochemical metabolization. Biochemical modulators not only can potentiate the antitumor activity and reduce the side effect of antitumor drugs but also can reverse the MDR in cancer cells. Based on the studies in our lab, several biochemical modulators were found and their mechanisms of synergetic effect with chemotherapeutic agents were studied.1. Potent cytotoxicity of LDM to MDR cancer cells.It was proved by MTT assay that LDM had highly potent cytotoxicitiy toward various cancer cell lines, including MDR and HER-2/neu overexpressing ones. The IC₅₀ values of LDM in these cells ranged between 10^-4 to 10^-6 μ M, which is much...