| Summary: | 碩士 === 慈濟大學 === 藥理暨毒理學研究所 === 96 === Minocycline is one of the tetracycline derivatives, which are antibiotics indicated for the treatment of bacterial infections. Recently, tetracycline derivatives have been demonstrated to exhibit anticancer activity in lung, renal and thyroid cancers. In the present study, we used human bladder cancer cell line BFTC905, normal cell line CRL2299, SV-HUC-1 and H293, to investigate the anticancer effect of minocycline. In BFTC905 cell culture, minocycline exerted a dose- and time-dependent inhibition of cell proliferation over 24-48 hrs. The IC50 for the inhibition of proliferation was less than 20 μM. Concentrations of minocycline below 20 μM were without cytotoxic or antiproliferative effect in normal cell lines CRL2299, SV-HUC-1, and H293. Higher concentrations of minocycline (>50 μM) inhibited the proliferation of SV-HUC-1, H293, and CRL2299 cells with the former exhibiting higher sensitivity. These results revealed the higher cytotoxicity of minocycline toward cancer cells. Minocycline at 20 μM enhanced the expression level of phospho-AKT in BFTC905 cells as early as 6 hrs after treatment, reflecting a surviving strategy for these cancer cells under stress. The expression of survivin was reduced transiently at 6 hrs after treatment. In contrast, the expression of caspase-3 and phospho-p38 was increased steadily with significant changes. Forty-eight hours after 20 μM minocycline treatment, apoptotic BFTC905 cells were increased with statistical significance measured by flowcytometry. Necrotic cell were also observed in DNA ladder under the same condition. The results may provide a new strategy for bladder cancer treatment.
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