| 研究生: |
鄭金松 Zheng, Jin-Song |
|---|---|
| 論文名稱: |
Youngia japonica的抗癌活性研究 An investigation on the antitumor activities of aYoungia japonica |
| 指導教授: |
李益謙
Li, Eric I-chian |
| 學位類別: |
碩士 Master |
| 系所名稱: |
醫學院 - 藥理學研究所 Department of Pharmacology |
| 論文出版年: | 2005 |
| 畢業學年度: | 93 |
| 語文別: | 中文 |
| 論文頁數: | 77 |
| 中文關鍵詞: | 抗癌 、黃鵪菜 |
| 外文關鍵詞: | Youngia japonica, antitumor activities |
| 相關次數: | 點閱:148 下載:1 |
| 分享至: |
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Youngia japonica (L.) DC,俗稱Oriental hawksbeard 或 Asiatic hawksbeard,是一種一年生或二年生草本。目前已有報導從Youngia japonica中分離出一些化學成分,例如sesquiterpene lactones和triterpene hydroperoxide。已有文獻指出,Youngia japonica水萃取物具有抑制human promyelocytic leukaemia (HL-60), human myelogenous leukaemia (chronic K-562) and mouse Sarcoma 180 (S-180)等三株癌細胞株之生長。而於離體外(in vitro)、活體內(in vivo)詳細的抗癌活性則未被研究。我們因而想進一步探討Youngia japonica粗萃取物(以下簡稱YJE),於離體外(in vitro)和活體內(in vivo),可能產生的抗癌活性。
於一序列離體外(in vitro)細胞毒殺實驗,Youngia japonica萃取物(YJE)可抑制ML1-4a、PC3、LLC、B16F10等多種癌細胞株的存活能力,且具劑量正相關性;但對於正常細胞株-BAEC並無太大的效果。另外YJE亦可促進5-Fu抑制PC3及B16F10癌細胞株的存活能力。進一步的,利用流式細胞儀(FACScan),以PI染色觀察YJE對細胞週期影響,發現YJE可促使B16F10 sub-G0/G1期細胞量增加。之後,再以Hoechst 33258進行細胞核染色觀察細胞核濃染現象,結果顯示YJE處理之後,癌細胞趨向程式死亡。於in vivo利用Balb/cj小鼠背部注射ML1-4a原位瘤模式及C57BL/6NCrj小鼠背部注射LLC原位瘤模式,發現YJE在活體中具有抑制癌細胞生長的能力。另外,於小鼠LLC原位瘤模式中亦發現,YJE可促進cisplatin抑制腫瘤生長作用。另一方面,我們也發現YJE具有抑制PC3癌細胞受化學驅化物誘導所產生的細胞移行以及降低PC-3分泌MMP-9,另外亦可抑制B16F10癌細胞癒合(wound healing),推測YJE可能具抑制腫瘤細胞轉移的能力。YJE也可抑制BAEC受胎牛血清誘導所產生的細胞移行和抑制內皮細胞從大鼠主動脈移行出,以及用雞胚胎絨毛膜試驗(chorioallantoic membrane assay)發現YJE在半活體(semi in vivo)內具有抑制血管新生的效果。進一步地,將腫瘤取下,測定其腫瘤中血紅素含量亦證明YJE在活體(in vivo)內具有抑制腫瘤血管生成的效果。
YJE僅為Youngia japonica的粗萃取物,其中所含的物質繁多,作用也較繁雜需要進一步探討更明確的分子機轉;尋找出有效的化學成分來進行分析。
Youngia japonica (L.) DC (Oriental hawksbeard or Asiatic hawksbeard in its folk name) is a biannual common weed from which several compounds have been identified, such as sesquiterpene lactones and triterpene hydroperoxide. Previous research indicated that aqueous extract obtained from Youngia japonica possess in vitro anti-tumor activity against three cell lines-human promyelocytic leukaemia (HL-60), human myelogenous leukaemia (chronic K-562) and mouse Sarcoma 180 (S-180). However, no animal experiments and other aspects of anticancer activities of Youngia japonica have been tested. Our study aims at investigating the anticancer activity of a crude extract obtained from Youngia japonica, which we termed YJE.
The extract shows markedly dose-dependent cytotoxicities against several cancer cell lines but no effect on the normal bovine aortic endothelia cell. YJE enhances cytotoxicity of 5-Fluorouracil (5-Fu) against cancer cells. The flow cytometry assay reveals that cancer cells death is due to apoptosis, which is supported by one more assay- Hoechst 33258 nucleus staining. The anticancer activity of YJE was investigated further in vivo using mouse bearing transplanted tumor cells. YJE significantly inhibits the growths of tumors both in the Lewis lung carcinoma and ML1-4A hepatoma animal models. In addition, YJE enhances cisplatin against Lewis lung carcinoma. Furthermore, we found YJE inhibits the migration toward chemoattractant and reduces MMP-9 of human prostate cancer cells (PC-3) and inhibits wound healing of B16F10 cells, suggesting YJE possesses an anti-metastatic principle. YJE also exhibits anti-angiogenesis activities in an endothelia cell migration assay, endothelia cell migration from rat aortic ring as well as blood vessel formation in a semi in vivo chicken chorioallantonic membrane (CAM) assay. Besides, YJE reduces the hemoglobin contents of LLC primary tumors from YJE- treated mice, indicating the tumor-inhibiting activity is due to the inhibition of angiogenesis.
The active anticancer ingredient and its detailed molecular action mechanism in Youngia japonica warrant further investigations.
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