| The research of epidemiology reveals that aspirin can reduce the incidence of colon cancer. It is known that aspirin inhibits the growth and proliferation of the cell lines of colon cancer through the inactivation of COX-2 activity. However, it is also known that not all the colon cancer cells express COX-2. So far, there have been only limited numbers of studies on the function of aspirin in the COX-2 deficiency tumor cells. Some studies reveal that aspirin activates the p38MAPK to inhibit the growth and proliferation of COX-2 negative colon cancer cells. The SOX family of transcription factors is found in animals in recent years. The product of SOX has a HMG domain conservation, which plays a role in sex determination, hematopoiesis, and development of bone tissue, nervous system, crystalline lens, lung and heart, as well as in multiple process of early embryogenesis. Some SOX genes are related with human diseases. SOX7 is a member of the SOX F subfamily. The analysis of mouse gene chips indicates that the mouse SOX7 may be the target gene of p38MAPK signal pathway. Experiments in this thesis indicate that aspirin can up-regulate the expression of SOX7 in SW480 cells, and interference of SOX7 expression can abolish the inhibitory effect of aspirin in SW480 cells. Blockage of p38MAPK signal pathway by treating 293T cells with specific inhibitor SB203580 suppresses the expression of SOX7 at mRNA level, demonstrating that human SOX7 may be the downstream target gene of p38MAPK signal pathway. The results from the luciferase report gene assays indicate that AP-1, which is a downstream transcription factor of p38MAPK signal pathway, can up-regulate the activity of SOX7 promoter. Our study reveals that SOX7 is involved in the inhibition of aspirin to SW480 cell growth, and aspirin may up-regulate the expression of SOX7 by activating the p38MAPK. This study lays down the foundation for further studies of the mechanisms of functions of aspirin and SOX7 in inhibition of colon cancer.
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