利用組合指數探討薏苡麩皮中抑制肺癌及結腸癌物質間之相互作用

Abstract

在過去二十年間，癌症一直是台灣十大死亡病因之一，其中肺癌和結腸癌更居十大癌症的第一和第三位。本研究以組合指數(combination index)來探討由本實驗室自薏苡麩皮甲醇萃出物分中所分離純化出之化學有效成分對抑制人類肺癌A549和結腸癌細胞HT-29生長的相乘作用或拮抗作用，探討各個活性成分之間的相互影響和作用關係。由兩種化合物組合的結果發現，咖啡酸(caffeic acid；PA4)或3-O-coumaroyl-β-sitosterol (PE1)與其他化合物組合時，對於抑制A549細胞增生方面有相乘的作用，另一方面，綠原酸(chlorogenic acid；PA6)與其他化合物組合時，有強烈的拮抗作用。而在抑制HT-29細胞增生方面，棕櫚酸(palmitic acid；FA )、5-hydroxy-7-methoxy-4’-acetylisoflavone (IF) 和豆脂醇(stigmasterol；S1)的兩兩組合間皆有相乘的作用。在這些純化合物中，細胞毒性會隨著試驗細胞的不同而產生不一樣的效果，所以組合時所產生的效力也不同。例如，PA4可與其他化合物產生抑制A549細胞增生的相乘效果，但在抑制HT-29細胞增生方面，PA4與IF或FA的組合則有拮抗的效果。由三種化合物組合的結果發現，PA4-PE1-IF組合 與 PA6-PE1-FA組合皆有最強抑制A549細胞增生的效果，而在抑制HT-29細胞增生方面，S1-IF-FA為最強相乘作用之組合。另外，PA4-PA6-IF組合皆對此兩種癌細胞有最強的拮抗作用。最後，在設計開發薏仁成為輔助抑制腫瘤保健食品時，須要針對不同的細胞來做不同的設計，以提高抑制癌細胞生長的效果。

The malignant tumor has continuously occupied the first place of the top ten leading causes of death for more than twenty years in Taiwan. Among those malignant neoplasm cases, the lung cancer and colorectal cancer are the first and third places of the top ten leading cancer, respectively. In this study, the combination index methodology was used to discuss the synergism or antagonism among these anti-tumor components from adlay bran. The result showed that caffeic acid (PA4) and 3-O-coumaroyl-β-sitosterol (PE1) appeared to be most synergistic compounds for combining with other compounds and chlorogenic acid (PA6) was the most antagonistic compound with other compounds on the growth inhibition of A549, a human lung cancer cell line; while any 2-compound combinations of palmitic acid (FA), 5-hydroxy-7-methoxy- 4’-acetylisoflavone (IF) and stigmasterol (S1) appeared to be synergistic on the growth inhibition HT-29, a human colorectal cancer cell line. Moreover, the cytotoxicity of compounds varied depending on the cell line tested and that such variation may in turn influence those effects of compound combinations. For example, in 2-compound combinations, PA4 exerted synergism when combining with other compounds to inhibit the growth of A549; while it became an antagonist toward other compounds, such as IF and FA, to inhibit the growth of HT-29. Moreover, in 3-compound combinations, the most synergistic 3-compound groups were PA4-PE1-IF and PA6-PE1-FA against A549 growth; while the most synergistic group was S1-IF-FA against HT-29 growth. On the other hand, the combination of PA4, PA6, and IF was the most antagonism on the growth inhibition of A549 and HT-29. From both cell lines, the results of the 3-compound combinations could be explained by the results of the 2-compound combinations. Last, the design of anti-cancer adlay supplement must be tumor-specific since that the cytotoxicity of the compounds varies depending on the cell line tested and that such variation may in turn influence those combined effects of the pure compounds.