Study of the inhibitory effect and its mechanism ofDioscorea nipponic Makino extract on melanoma cancer invasion and migration
| Autor: | Jia-Jing, 陳佳靜 |
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| Rok vydání: | 2009 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 97 Melanoma is a malignant tumor of melanocytes which are found predominantly in skin but also in the bowel and the eye. It is one of the rarer types of skin cancer but causes the majority of skin cancer related deaths with only approximately10-40% of a 5-year survival rate. Around 160,000 new cases of melanoma are diagnosed worldwide each year, and it is more frequent in males and Caucasians. It is more common in Caucasian populations living in sunny climates than in other groups. According to a WHO report about 48,000 melanoma related deaths occur worldwide per year. Malignant melanoma accounts for 75 percent of all deaths associated with skin cancer. The treatment includes surgical removal of the tumor, adjuvant treatment, chemo- and immunotherapy, or radiation therapy. Chinese medicinal herbs have been used for therapeutic purposes in traditional and folk medicine for a long time. In this study, we determined the effect of 99 herb extracts on cell migration; meanwhile, showed that 50% alcohol extracts of Dioscorea nipponica Makino (DNEs) could efficaciously inhibit melanoma cell migration and invasion by wound healing assay and Boyden chamber invasion assay. From this result, DNEs were chosen for the subsequent experiments. Dioscorea nipponica has long been used as a folk medicine for asthma, rheumatoid arthritis, bronchitis, and other diseases. These compounds have also been reported to be able to decrease serum lipids in cholesterol-fed rabbits. However, these studies on functions of Dioscorea nipponica have been mainly focused on the effects of anti-inflammatory, anti-obesity or anti-allergic property, whereas the effect of Dioscorea nipponica Makino on migration and invasion of tumor cells has not been clearly clarified. This study first demonstrates that, in the absence of cytotoxicity, DNEs exerted a dose-dependent inhibitory effect on the invasion, migration, and motility of highly metastatic murin melanoma cells (B16F10) and human melanoma cells (A2058). We examined the effect of DNEs on factors of cancer metastasis. We treated tumor cells with various concentrations of DNEs, for set periods, and then subjected cells to gelatin zymography, casein zymography, and Western blot to investigate the expression of matrix metalloproteinase-2 (MMP-2), urokinase-type plasminogen activator (u-PA), and tissue inhibitor matrix metalloproteinase -2 (TIMP-2). Following treatment with DNEs was found to decrease the expression of MMP-2 and u-PA in a concentration-dependent manner and enhance the expression of TIMP-2. To investigate the possible mechanisms involved in these events, we performed western blot analysis to find that DNEs inhibited phosphorylation of Akt. A treatment with DNEs to B16F10 cells also inhibited the activation of NF- kappa B as shown by Western blot and electrophoretic mobility shift assay (EMSA). Finally, DNEs were evidenced by its inhibition on the metastasis and tumor volume of B16F10 cells in vivo. Taken together, these findings suggested that DNEs could reduce the metastasis of murin melanoma cells, thereby constituting an adjuvant treatment for metastasis control. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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