魏淑2006-07-262018-07-112006-07-262018-07-112002http://ntur.lib.ntu.edu.tw//handle/246246/23547The “Vogelgram ” proposed by Vogelstein and his colleagues, described the adenoma-adenocarcinoma sequence, had mentioned the adenomatous polyposis coli (APC) gene mutation in the early stage of colorectal carcinogenesis. Mutation of the APC gene leads to abnormal epithelial proliferation and differentiation. -catenin can bind members of the Tcf/Lef family of transcription factors and activate gene transcription. C-MYC, cyclin D1 and matrix metalloproteinase-7 (MMP-7) were found to be the downstream targets of this  -catenin/Tcf-regulated transcription. It appears that c-MYC activation is a direct consequence of APC loss and thus a primary cause of tumor cell proliferation. Aspirin and/or nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the adenoma size and numbers in FAP patients. Disease prevention is receiving more attention in the developed country today. The risk-benefit ratio for chemoprevention of colorectal cancer would likely improve if high-risk groups could be identified and less side effect drugs could be used. COX-2 selective inhibitors and curcumin have less side effects than sulindac but their effects on colorectal cancer remained to be clarified. This study was designed to first realize the serial gene expression changes after sulindac treatment, especially focusing on APC,  -catenin, TCF, cyclin D1, MMP-7, axin-2 and c-MYC; and to second compare the anti-proliferation and apoptosis-inducing ability of sulindac, curcumin and COX-2 inhibitor. The results of this study revealed that Sulindac still remained the most constant effective (anticancer) agents among these three test compounds which has the effects of inducing cancer cells apoptosis and cell cycle paused at G1 phase effects. Curcumin has the effects of inducing cancer cells apoptosis and cell cycle paused at G2M phase. Lonine (Etolodac), a COX-2 inhibitor, has less apoptosis-inducing effects but can pause the cell cycle in G1 phase. All these effects were time and dose dependent. The Northern blot results showed that only c-myc expression decreased in HCT116 after sulindac treated for 48 hours but no significant changes of other genes. Further study is indicated for confirming the results.application/pdf184164 bytesapplication/pdfzh-TW國立臺灣大學醫學院內科SulindacCOX-2 inhibitorCurcuminColorectal carcinogenesis[SDGs]SDG3reporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/23547/1/902314B002220.pdf