1. The effect of aqueous extract of Prunella vulgaris in suppressing invasion and migration in human non-small cell lung cancer cells. 2. Identification of novel small chemicals with autophagic clearance of polyglutamine aggregation in human neuroblastoma cells.

100

1. Cancer cells grow and duplicate unregulated that form malignant tumors. The capability of cell invasion and migration from the origin site (metastasis) to nearby parts is the most threating. Cancer metastasis starts with the degradation of extracellular matrix (ECM). Both invasion to nearby tissue of cancer cell and inducement to angiogenesis relies on the matrix metalloproteinase (MMP) activity for ECM degradation. The thesis focused on treating cell lines, A549 (wild type p53 human adenocarcinoma), H460 (human large cell lung carcinoma) and H1299 (p53 deleted human adenocarcinoma) with Chinese herb medicine (CHM), and then detect changes of MMP-9 and MMP-2 activities by evaluating gelatin zymography. Both gelatin zymography and western blot to find out whether CHM can inhibit the MMP-9 and MMP-2 expression. The work is also to figure out whether MMP-9 and MMP-2 inhibition affects the migration and invasion capacity of the cancer cells. We have found that the aqueous extract of Prunella vulgaris can affects MMP-9 and MMP-2 activities in human lung carcer cells, and inhibit the invasion and migration of cancer cells. The other goal of this thesis is to find out new CHM‘s that are capable of inhibiting tumor angiogenesis and metastasis by evaluating MMP-9 and MMP-2 activities in human hepatocarcinoma cells. 2. Cells digest unwanted substance by autophagy, a procedure that could reuse building blocks from unwanted substances and clarify poisonous substance. The recycled substrate is covered by lipid bilayer, forming autophagsome that combines lysosome for digestion. Polyglutamine (polyQ) disease is a set of genetic disorder caused by the increased numbers of CAG or CUG repeats in some neurodegenerative diseases. Drugs that induced up-regulation of autophagy have been proved decrease the toxicity of polyQ aggregation in mouse model of Huntington’s disease. Thus, the autophagy-inducing drugs promise to be an effective therapy of polyQ diseases. The thesis used SK cell lines transfected with green fluorescent protein conjugated with different length of polyQ. The purpose is to find out whether the autophagsome can be increased by treatment of different compounds and whether they affect the viabilities of the cells. Three compounds were found capable of inducing cell autophagy and decreasing polyQ aggregration in cell models. In the future, the research will focus on how the selected drugs affect autophagy and test the drugs in animal model.