碩士 / 國立臺北科技大學 / 生物科技研究所 / 102 / KRAS or BRAF mutation has an important role in the epidermal growth factor receptor pathway (EGFR pathway). According to our pervious findings, up-regulation of the expression of miR-378 by lauric acid in KRAS or BRAF mutant CRC (Colorectal cancaer) cells will further trigger the cell’s sensitivity of anti-EGFR antibody. Herein, we replaced the lauric acid (saturated fatty acid) by EPAee (unsaturated fatty acid), an FDA-approved compound, and used CRC cells as a model for this study. Our studies showed that higher expression of miR-378 could be observed in KRAS mutant CRC cells treated with 40 μM EPAee; besides, the total ERK1/2 protein levels of KRAS mutant CRC cells and wild type CRC cell were shown lower expression level (p=0.022~0.035) after treating cells with 40 μM EPAee for 24 hours, while the higher phosphorylated proteins level of ERK1/2 could be noted (p=0.006~0.047); but opposite result was shown in BRAF mutant cell. Interestingly, cells treat with 40μM EPAee fed for 24 houes and then anti-EGFR antibody for 48 hours, showed the lower cell viability in the KRAS mutant and control wild type cells (p= 0.006~0.013); but cannot improve the sensitivity of anti-EGFR antibody in EPAee-fed BRAF mutant cell. Indeed, using EPAee induce the over expression of miR-378 could further restore the sensitivity of anti-EGFR antibody in KRAS mutant cells. Although the molecular mechanism of the effect of EPAee in CRC cells is still not clear. Our findings have offered a great potential for developing a new treatment method for KRAS mutant CRC patients.
| Identifer | oai:union.ndltd.org:TW/102TIT05111001 |
| Date | January 2014 |
| Creators | Li-Wei Kuo, 郭力瑋 |
| Contributors | Wen-Hui Weng, 翁文慧 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 64 |
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