| Summary: | 碩士 === 國立陽明大學 === 生物藥學研究所 === 99 === Thalidomide is a potent antiangiogenic drug for cancer therapies. The molecular mechanism of thalidomide was proposed to inhibit the transcription of target genes by binding to the GC promoter sites. It has been demonstrated that the promoters of bFGF and IGF-I genes contain GC rich region. We proposed that the antiangiogenic activity of thalidomide may due its effect on downregulating the expression of bFGF and IGF-1. In our studies, we showed that thalidomide at the concentration of 0.01-10 ?慊/ml significantly diminished the expression of bFGF and IGF-1 in A549 cells. We also found that the liposome encapsulated thalidomide may prevent its rapid hydrolysis and prolong the inhibitory effects. Interestingly, our data showed that thalidomide efficiently inhibited the anchorage independent growth of A549 cells but not affect the proliferation. Furthermore, the in vitro migration models also showed that thalidomide treatment significantly reduced the migratory capacity of A549 cells.
Recent clinical studies suggest that there may be a direct link between cancer stem cells and metastasis. To validate the correlation between anchorage independent growth and cancer stem cells, we have further established the culture method to isolate sphere cells with anchorage independence ability, and characterize the properties of stemness. We founded that the AIG-selected cells display higher efficiency of colony formation and expression of stemness compared to monolayer cells. Our results further founded that thalidomide treatment dramatically suppressed the anchorage independent growth of these sphere cells. Accordingly, our data suggested the possibility of thalidomide targeting the cancer stem cell like cells.
In conclusion, we showed that thalidomide has the inhibitory effect on anchorage independent growth and tumor metastasis. These results suggested that anchorage independent growth and cancer stem cells might be potential targets for anti-cancer drug development. Hence, the role of GC rich genes in cancer stem cells and metastasis could be an interest target for further study. Our studies may have the important implications for development of effective cancer therapy, and provide the framework for new treatment strategies targeting presumptive cancer stem cells and metastasis.
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