| Summary: | 碩士 === 國防醫學院 === 微生物及免疫學研究所 === 103 === Colorectal cancer is the third most common malignancy and the fourth largest cause of cancer mortality. The reason why colorectal cancer causes such high mortality is that cancer cells may become resistance to chemotherapy and metastasize to other organs in late stage. Epithelial-Mesenchymal Transition (EMT) has been reported in many advanced cancers, and contributed to tumor progression by promoting tumor invasion, metastasis, and drug resistance. Snail is a transcription factor that mediates EMT in several tumor types, including colorectal cancer (CRC). Overexpression of Snail could induce EMT and acquire chemoresistance. Moreover, mutant form of Snail could have better effect on enhance drug resistance and induce EMT. Epigenetic regulation plays an important role in EMT and drug resistance in many malignant cancers. However, DNA methylation profile in this process remains unclear. In our proposal, we want to study whether abnormally methylated genes play important roles in the drug resistance in CRC cells with EMT phenotype.
In this study, we have established a SNAIL1-overexpressing CRC cell line, and. Overexpression of Snail in HT29 did not affect cell viability, but significantly increased drug resistance and migration ability.Similar phenomen was shown in SNAIL1-overexpressing SW480 CRC cells. EMT could be induced by Snail has been reported in advanced cancers, and contributed to tumor progression by promoting tumor invasion. Therefore, we analyzed the mRNA level of EMT markers by Q-PCR and western blot. Snail could increase mesenchymal markers and decrease epithelial markers, such as, OCLN1, FN1, and CDH1. Furthermore, Snail could increase CCND1 expression. Moreover, we also found that Snail is not mutated in three CRC cells. Previous studies have shown that Snail may regulate downstream genes through epigenetic modification and promote cancer progression. Till Now, our preliminary data found that Snail did not affect the promoter methylation level of FN1 and CCND1 by methylation specific PCR(MSP). Whether Snail may regulate downstream genes through epigenetic modification (such as DNA methylation or histone modification) involved in drug resistance of CRC needs further investigation.
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