Summary: | 碩士 === 國立陽明大學 === 藥理學研究所 === 91 === Abstract
IARC stated in 1985 that chewing areca quid with tobacco could
lead to oral cancer. Many epidemiological studies indicated that chewing areca quid alone also correlated to the development of oral cancer in Taiwan. Polyphenols, the major components of areca nut, causes the astringent taste while chewing areca quid. Lime is added to areca quid to quench it but also can cause an alkaline environment to generate free
radical. Recently it was found that fractionated ripe areca nut extracts (Fr. rANE) had more cytotoxic effects on OEC-M1 and OC-3 oral cancer cells under alkaline condition than cells cultured in normal medium.
Using cDNA microarray technique, it was observed that the expression of several genes, including vascular endothelial growth factor-D (VEGF-D) and Interleukin-8 (IL-8) were down regulated after treatment of OEC-M1 cells with 50μg/ml Fr. rANE. This study then tested the effects of Fr. rANE on the expressions of VEGF-D and IL-8 in oral cancer cells by real-time PCR. The results demonstrated that Fr. rANE decreased the
gene expressions of VEGF-D and IL-8 in OEC-M1 oral cancer cells in a dose-dependant manner. However in wild-type p53 OC-3 oral cancer cells, Fr. rANE increased the gene expressions of VEGF-D and IL-8. The VEGF-D mRNA expression was dramatically increased after treatment with 200μg/ml of Fr. rANE. The extracellular parameter pH values had no effect on the Fr. rANE modulation of VEGF-D and IL-8 gene expression in neither OEC-M1 nor OC-3 cancer cells. It is known that SC-M1 gastric cancer cells can secrete high levels of VEGF (1747.27 pg/ml) and express VEGF-R2 on its cell surface. Therefore, SC-M1 cells were used as a positive control to examine the effects of Fr. rANE and EGCG (a well-known angiogenesis inhibitor on the expression of VEGF-D and IL-8). Fr. rANE can modulate the VEGF and IL-8 gene expression as EGCG. Taken together, these results suggested Fr. rANE might have alternative effect for angiogenesis research.
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