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標題: | 羌活抑制肝癌細胞的轉移與增生 Notopterygii Rhizoma Suppresses the Migration and Proliferation of Hepatocellular Carcinoma Cells |
作者: | Ya-Yueh Pang 龎雅月 |
指導教授: | 林榮耀 |
關鍵字: | 肝細胞癌,羌活,轉移,增生,C/EBP,表皮生長因子受體,血管內皮生長因子受體, Hepatocellular carcinoma,Notopterygii Rhizoma,Migration,Proliferation,C/EBP,EGFR,VEGFR-2, |
出版年 : | 2011 |
學位: | 碩士 |
摘要: | Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality with 600,000 deaths annually. HCC is usually caused by some risk factors including hepatitis virus infection, aflatoxin-B1-contaminated food and chronic alcohol consumption. Some of molecularly targeted drugs are used to treat patients with advanced HCC such as Sorafenib, Sunitinib and Brivanib. However, the recurrence rate of HCC remains high due to the metastasis ability of cancer cells. Therefore, it is an urgent issue to discover novel therapeutic agents that can inhibit tumor formation and metastasis.
In recent years, Chinese Herbal Medicines (CHMs) are widely used as alternative medicines in the treatment of cancers. Notopterygii Rhizoma (NR), one kind of CHMs, is currently used for treating various inflammatory diseases including rheumatoid arthritis and relieving pain. In the present study, we examined the inhibitory effects of three CHMs (Notopterygii Rhizoma, Gardenia Jasminoides, Je Chung Yin) on cell migration and prolferation on Hep3B cells by transwell migration assay and MTT assay. We found that the aqueous extracts of NR significantly inhibit cell proliferation and migration of HCC cells in vitro and in vivo. NR suppresses the migration activity of Hep3B cells with a medium inhibitory concentration (IC50 migration) value sixteen times lower than that of proliferation activity (IC50 cytotoxicity). In vivo efficacy of NR was measured by subcutaneous tumor xenografts and tail vein injection in NOD-SCID mice. Daily oral administration with NR significantly inhibited the growth of tumor xenografts and lung metastases. By luciferase reporter assay, NR inhibits cancer cell proliferation and migration via blocking C/EBP-mediated transcriptional regulation which leads to inhibit EGFR and VEGFR-2 downstream signaling pathways significantly. Furthermore, NR suppresses the ERK/MAPK pathway to decrease the expression of ICAM-1 as shown by quantitative real-time PCR and western blotting analysis. In addition, NR suppresses the translocation of β-catenin and Slug into the nuleus resulted in inhibiting the transcription of N-cadherin, one of the cell-cell adhesion glycoproteins. Moreover, NR diminishes the activation of Rac-1 and Cdc42, the Rho GTPase family members, as demonstrated by pull down assay. It was further demonstrated NR suppresses the activation of Rac-1 and Cdc42 via FAK/Src pathway resulting in disruption the formation of actin filaments. Besides, we observed that NR causes cell cycle G1 phase arrest in HCC cells. The treatment of NR decreases the mRNA and protein levels of Cyclin D1 through the down-regulation of β-catenin and ERK pathways, and suppresses the protein levels of CDK4, Cyclin B and CDK1 in HCC cells. Taken together, Notopterygii Rhizoma may be a potential chemotherapeutic agent for the treatment of HCC. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/24597 |
全文授權: | 未授權 |
顯示於系所單位: | 生物化學暨分子生物學科研究所 |
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