| Summary: | 碩士 === 國立臺灣大學 === 食品科技研究所 === 101 === Colorectal cancer (CRC) is the major cancer which causes people dead worldwide. In Taiwan, according to the Bureau of Health Promotion, Department of Health, CRC has reached the first place in cancer incidence. Tumor cell metastasis is the most malignant feature during cancer progression and accounts for the major factor (90%) of mortality.
Current cancer treatment includes surgery and chemotherapy, but there are still side effects and recurrence problems. Therefore, nowadays medicine profession pays more attention to the research and development of traditional Chinese herbal medicines (TCM). As a Consequence, our aim was to find the potential TCM to decrease the metastastic rates of colorectal cancer.
In our study, we used the colorectal cancer cell line, SW620, which has high metastasis ability for in vitro assays. We also chose 13 pure compounds, which have the potential for anti-metastasis, from TCM based on the literatures to investigate the anti-metastastic ability of those pure compounds and the possible mechanism. The pure compounds include Andrographolide, Evodiamine, Curcumin, Wogonin, Baicalein, Baicalin, Chrysin, Triptolide, Celastrol, Magnolol, Honokiol, 6-gingerol and 6-shogaol.
There are three phases of our experiments. In phase one, we tested the ability of anti-proliferation of those pure compounds by MTT assay. Then we selected curcumin (Cur) and honokiol (Hon), which are more effective than the others, to conduct bioactivity test.
In the second phase, we used would-healing assay and Boyden chamber assay to analyze the potential of anti-migration and anti-invasion of Cur and Hon. Results showed that both of Cur and Hon had the inhibitory ability of anti-migration on SW620 in a dose-dependent manner. Besides, they also effectively reduced cell invasion. The inhibition rates of the treatments of different concentration of Cur (5, 10, 30μM) were 65%, 69% and 93%. For Hon, they were 40%, 70% and 69%. The data demonstrated that both of Cur and Hon could suppress the metastasis of SW620.
Finally in phase three, we investigated the possible mechanism of the anti-migration effect of Cur and Hon. Using western blotting assay, we found that although Cur and Hon could not decrease MMP2 and MMP9 expression, they could significantly inhibit active and pro-form MMP7 protein expression with dose-dependency. Moreover, both of Cur and Hon could augment the expression and stability of E-cadherin proteins on the cell membrane to prevent the disruption of cell contacts. They could also avoid β-catenin to translocate into nuclear binding downstream targets such as MMPs (especially MMP7) thus downregulated cell metastasis.
In conclusion, our findings suggest that Cur and Hon could maintain the expression of E-cadherin on cell membrane, avoid β-catenin translocation and then suppress the translation of MMP-7 protein, thus inhibit the metastasis of human colorectal cancer cell line SW620.
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