評估皿培牛樟芝子實體抑制肝癌細胞及以D-氨基半乳糖誘發肝細胞損傷保護之效果

Abstract

牛樟芝為台灣民俗的珍貴藥用真菌，經常被用於治療肝臟疾病、高血壓、腹痛、腹瀉或其它疾病；近年來有關牛樟芝的研究大多著重於多種人類癌症的治療以及保護肝臟免於酒精及病原感染等所造成的損傷。肝炎病毒感染目前被認為是造成肝癌的最主要成因，其次為酗酒，由於難以早期診斷，且不易進行手術，以及缺乏有效治療藥物，導致肝癌患者的死亡率及復發率都很高。為開發具有保護肝臟及治療功能的藥物，以補足傳統治療的不足，本研究將評估牛樟芝皿培子實體的酒精初萃物保護肝臟細胞以及抑制肝癌細胞的效果。我們的研究結果顯示，本初萃物能夠有效抑制HepG2及HA59T兩個肝癌細胞的增生及降低其存活率，並且使肝癌細胞的細胞週期停滯於G2/M期，同時也抑制肝癌細胞遷移及侵潤等腫瘤細胞的癌化特性。此外，我們給與初代培養的大鼠肝細胞及肝細胞株(Clone 9) D-氨基半乳糖(D-galactosamine)來模擬肝細胞功能的損傷，結果發現給與D-氨基半乳糖降低了肝細胞製造白蛋白(在基因及蛋白質層級)、合成尿素及表現解毒酵素細胞色素的能力，而投與本初萃物能有效逆轉因D-氨基半乳糖所造成的肝細胞功能損傷。總結本研究的成果發現，本研究所使用之皿培牛樟芝子實體酒精初萃物能有效抑制肝癌細胞的癌化特性，同時保護肝細胞免於因D-氨基半乳糖所造成的肝功能損傷。

Antrodia cinnamomea (AC) is a treasured endemic Taiwanese medicinal mushroom and is used to treat liver diseases, hypertension, abdominal pain, diarrhea, and other diseases. Recent studies related to AC focused on the treatment of various cancers and protection against liver injuries causing by alcohol and pathogen infection etc. Hepatocellular carcinoma (HCC) accounts for 70–85% of the total liver cancer burden and usually develops within a background of advanced chronic liver disease, mainly related to infection of hepatitis virus and alcohol abuse. Mortality and recurrence rate of liver cancer remains high because of the difficulty of early diagnosis, hard operation and lack of useful therapeutic drugs. To develop alternative or adjuvant treatments for improving the clinical outcome of the conventional therapy, ethanol extract of dish-cultured AC fruiting body was used to evaluate its antitumor and hepatoprotective effects. The result showed that AC treatment inhibited proliferation and reduced viability of both human HCC cells, HepG2 and HA59T, and arrested the cancer cells in the G2/M phase of cell cycle. At the same time, AC treatment also inhibited their migration and invasion which is the malignant characteristics of cancer cell. Furthermore, application of D-galactosamine (D-gal) damaged the functions of rat liver cells, Clone 9, and rat primary liver culture cells on albumin production (in mRNA and protein levels), urea synthesis and cytochrome P450 expression. The addition of the AC protected liver cells from those injuries caused by D-gal. In conclusion, the ethanol extract of dish-cultured AC fruiting body inhibited malignant characteristics of HCC cells while protected liver from injury caused by D-gal.