| 摘要: | 異常的血管增生會造成癌症、糖尿病失明、與年齡相關的黃斑部病變、類風濕關節炎、牛皮癬等疾病，其中又以癌症最為嚴重。根據我國衛生福利部的統計資料顯示，癌症已連續33年蟬聯國人十大死因第一名。癌症致死率高與缺乏有效治療癌細胞轉移有密?關係，癌細胞的轉移過程分成血管增生（Angiogenesis）、移行（Invasion）和入侵（Migration）三大步驟。5氟尿嘧啶（5-Fluororacil, 5-FU）是目前臨床治療癌症常用的化療用藥，它雖然可以抑制癌細胞的增生和轉移，劑量高時隨之而來的副作用卻讓患者難以耐受。研究發現類茄紅素（LycogenTM）是透過Rhodobacter sphaeroide改良菌株順利大量生產與茄紅素結構類似之物質，已進一步取代茄紅素（Lycopene）缺點（取得不易與高成本）。研究發現類茄紅素具有顯著的美白、防皺、抗老化與抗發炎的功效，然而是否可以抑制血管增生並不清楚。因此，本研究的主要目的是要探討類茄紅素與臨床用藥5-FU是否可以產生協同作用進而減少使用量，使治療的副作用相對減少，對於癌症患者的預後和生活品質也可達到更好的結果。本實驗以EA.hy926（人類內皮細胞）來進行研究，EA.hy926細胞是人類臍靜脈內皮細胞（Human umbilical vein endothelial cells, HUVEC） 與人類肺腺癌細胞（A549）的融合細胞，它常被拿來做細胞血管增生、入侵、移行及高血壓等相關研究。我們以MTT assay、tube formation assay、cell invasion assay、cell migration assay及 zymography assay來測定類茄紅素對EA.hy926細胞的細胞存活率分析、脈管增生的抑制、入侵及移行的抑制及MMP-2的活性。結果顯示，類茄紅素在10 μM時不僅可以單獨抑制EA.hy926細胞脈管增生、入侵（45％）、移行（40％）、及MMP-2活性，合併5-FU時與單獨類茄紅素處理時相比亦可加強5-FU抑制EA.hy926內皮細胞的移行和入侵分別達 1.2倍及1.3倍的加乘效應。故我們推測類茄紅素具有輔助5-FU開發為保健食品之潛力。
Abnormal vascular proliferation can cause cancer, diabetes, blindness, age-related macular degeneration, rheumatoid arthritis, psoriasis and other diseases, among which, cancer is most serious. According to statistics results of the Ministry of Health and Welfare show that the cancer has been 33 consecutive years ranked the first one among the top ten causes of death. Cancer death rate is always high. The lack of effective treatment on cancer metastasis is main cause to worsen the patient’s condition. The metastasis of cancer cells can divide into angiogenesis, invasion and migration, three major steps. 5-Fluororacil (5-FU) is a kind of commonly chemotherapy drugs used in clinical treatment of cancer. Although it can inhibit cancer cell proliferation and metastasis, high doses usage can cause the attendant side effects in patients and difficult to tolerate. The previous study found that lycopene class (LycogenTM) is a smooth mass production of lycopene and structurally similar substance through the Rhodobacter sphaeroide improved strains have been further substituted lycopene (Lycopene) shortcomings (difficult to obtain and costly). The previous studies found that LycogenTM has significant class whitening, anti-wrinkle, anti-aging and anti-inflammatory effect. However, effects of LycogenTM on inhibition of angiogenesis is still not clear. Therefore, the main objective of the present study is to investigate whether LycogenTM and clinical drug 5-FU can produce a synergistic effect via reducing the amount of use, or the relative reduction of side effects of treatment, and the prognosis for cancer patients can achieve a better quality of life the result of. In this experiment, EA.hy926 cell (human umbilical vein endothelial cells Human umbilical vein endothelial cells (HUVEC) and human lung adenocarcinoma cells (A549) fused cells) are used, they are often used as a research cell for angiogenesis, invasion, migration and hypertension. The methods our used in this study are MTT assay, tube formation assay, cell invasion assay, cell migration assay and zymography assay and to estimate the situations of AEWA on cell viability with EA.hy926 and inhibiting vascular proliferation, invasion and migration via inhibiting and MMP- 2 activity. The results show that LycogenTM at 10 μM can inhibit vascular EA.hy926 cell proliferation, invasion (the rate value is 45%), migration (the rate value is 40%), and MMP-2 activity. when treatment accompanied with 5-FU can help to enhance effectiveness of inhibition compared to single giving with 5-FU in EA.hy926 endothelial cell migration and invasion. Therefore, we hypothesized that LycogenTM has the potential to assist the effect of 5-FU to the health food. |
