| Summary: | 碩士 === 中臺科技大學 === 食品科技研究所 === 97 === Berberine, a compound isolated from medicinal herbs, has been reported to that many pharmacological effects related to anti-cancer and anti-inflammation capabilities. we chose cervical cancer cell line : Ca Ski, HeLa, Si Ha cells treated with various concentration of berberine to probe into the potential of inhibiting cancer-cell invasion. We assayed the cell viability, cell invasion/motility, matrix metalloproteinases (MMPs) activity, and urokinase-plasminogen activator (u-PA) activity of Ca Ski, HeLa, Si Ha cells with flavonoid treatments by MTT assays, invasion/motility assays, gelatin zymography, and casein zymography. We found that berberine significantly inhibited the cell invasion/motility capacities and the activities of MMP-2 and u-PA in Ca Ski, HeLa, Si Ha cells without affecting cell viability. Following treatment with these compounds was found to decrease the expression of MMP-2, MMP-9, and u-PA in a concentration-dependent manner and enhance the expression of TIMP-2 and PAI-1. Further, a treatment of berberine also resulted in an inhibition of the activation of p-JNK1/2 and p-p-38. In order to confirm whether the activation of above proteins regulates Si Ha invasion ability, we used specific inhibitors: SB253080 and SP600125 to clarify that JNK1/2 and p38 signaling regulate MMP-2 expression, cell motility and cell invasion of Si Ha, and JNK1/2 signaling regulate MMP-2, u-PA expression and cell invasion. Finally, an in vivo anti-tumor study using nude mice (BALB/c nu/nu) xenograft model by a subcutaneous inoculation of Si Ha cells was performed. The average tumor volume of treatment groups was statistically lower than that of the control group. In conclusion, berberine may be a powerful candidate for a preventive agent against cervical cancer development.
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