- 學位論文
比較不同天然植物萃取液 對急性骨髓性血癌之抑癌作用
To Compare the Anti-tumor Effects of Different Plant Extracts in Acute Myeloid Leukemia
摘要
急性骨髓性血癌(Acute myeloid leukemia, AML)為血癌四大分類之一，其主要患者群為中老年齡階層，目前臨床上常用之治療方法為化療，但對中老年階層患者之效果不彰，有高副作用、高死亡率高及低治癒率等缺點，因此針對年長族群的AML患者群而言，尋找新的治療藥物是具有其臨床需求性。在極少數文獻證實，於體外試驗中，部分腫瘤細胞株經過廣藿香萃取液(Pogostemon cablin, PPa)及雪松萃取液(Cedrus atlantica, CAt)處理後，發現腫瘤細胞生長受到抑制，但其詳細機制仍未探討。本論文研究目的為比較不同天然植物萃取液對AML之抑癌作用。在實驗結果中，CAt有較佳之抑制血癌細胞生長之情形相較於PPa之作用，而與臨床藥物Cyclophosamide相比較，PPa及CAt皆有較好之抑制效果且對正常細胞毒性較低。從細胞週期分析可知，PPa及CAt皆會誘發細胞週期停滯在G0/G1時期且Sub-G1之百分比增加。進一步以TUNEL assay觀察到細胞染色質濃縮、DNA斷裂及細胞凋亡小體產生之細胞凋亡相關型態。在分析細胞凋亡相關蛋白表現量，PPa及CAt能誘發Caspase-3、Caspase-8活化態之表現量增加及Procaspase-9之表現量下降以促使細胞進行凋亡。在血管新生及腫瘤轉移相關蛋白表現量，PPa及CAt皆能抑制血管新生相關蛋白及腫瘤轉移相關蛋白表現。因此可知經由PPa及CAt處理後，皆能提高抑制AML生長及誘發細胞凋亡，具有做為治療血癌之臨床性輔助藥物之開發潛力。
並列摘要
Acute myeloid leukemia (AML) is one of the four major leukemia types, its main patient age is elder population. Current clinical therapy for AML is chemotherapy, but it contains lots of disadvantages against treating elder people, including high side-effect, high mortality and low cure rate. Futhermore, it’s necessary to find a new therapeutic drug for all AML patients and clinical demand. Rare reports have shown that partial tumor cells growth were inhibited after treaing with Pogostemon cablin (PPa) and Cedrus atlantica (CAt); their mechanisms are still unknown. In this study, PPa and CAt not only showed better growth inhibition after treatment in HL-60 cell, but also showed much less cytotoxic effect in normal cell lines. In cell cycle analysis, we found that HL-60 cell after treating with PPa and CAt could induce cell cycle arrest at G0/G1 phase and increase persantages of sub-G1. It also could trigger extrinsic and intrinsic cell apoptosis pathway causing cell death. PPa and CAt also had anti-agiogenesis and anti-metastasis effects in vitro. In conclusion, PPa and CAt could induce cell cycle arrest, cell apoptosis, anti-angiogenesis and anti-metastasis effects; they will be potential anti-cancer agents in AML therapy.