Li Shun-Lai, Huang Zih-Ning, Hsieh Hsiao-Hui, Yu Wen-Chun, Tzeng Win-Yu, Lee Guo-Yang, Chen Yi-Peng, Chang Chia-Yu, Chuu Jiunn-Jye
Institute of Biotechnology, College of Engineering, Southern Taiwan University, Yung-Kang City, Tainan, Taiwan.
Am J Chin Med. 2009;37(4):771-83. doi: 10.1142/S0192415X09007235.
Antrodia camphorata, unique fungal specie, has been used as a folk medicine in Taiwan for many years. The purpose of this study was to compare the extracts from the solid-state culture of A. camphorata co-fermented with Chinese medicinal herb (AC-CF) with two other extracts from fruiting bodies (AC-FB) or solid-state culture (AC-SS), for their anti-tumor effects in human hepatoma HepG2 cells. We measured in vitro cell proliferation, percentage of apoptosis, population distribution of cell cycles, Western blot analysis of multiple drugs resistance-1 (MDR-1), and apoptosis-related proteins in HepG2 cells treated with three different preparations of A. camphorate extracts. Our results showed that AC-CF had better anti-proliferation effect on human hepatoma HepG2 cells than AC-FB or AC-SS dose-dependently. In addition, AC-CF in combination with anti-tumor agents (mitomycin C or methotrexate) showed better adjuvant anti-tumor effects than AC-FB or AC-SS. We further demonstrated the augmented adjuvant anti-tumor effects of AC-CF not only through down regulation of MDR-1 expression but also through a COX-2 dependent apoptosis pathway, involving down-regulation of COX-2 and p-AKT and up-regulation of PARP-1. In conclusion, in this study, we have demonstrated a novel strategy of fermenting A. camphorata with Chinese medicinal herb (AC-CF), which augmented their anti-tumor effects in human hepatoma HepG2 cells as compared to the traditional ones (AC-FB or AC-SS).
樟芝，一种独特的真菌物种，多年来一直在台湾被用作民间药物。本研究的目的是比较樟芝与中药材共发酵固态培养物提取物（AC-CF）与另外两种来自子实体（AC-FB）或固态培养物（AC-SS）的提取物对人肝癌HepG2细胞的抗肿瘤作用。我们测量了用三种不同制剂的樟芝提取物处理的HepG2细胞的体外细胞增殖、凋亡百分比、细胞周期群体分布、多药耐药-1（MDR-1）的蛋白质免疫印迹分析以及凋亡相关蛋白。我们的结果表明，AC-CF对人肝癌HepG2细胞的抗增殖作用比AC-FB或AC-SS具有剂量依赖性。此外，AC-CF与抗肿瘤药物（丝裂霉素C或甲氨蝶呤）联合使用时，显示出比AC-FB或AC-SS更好的辅助抗肿瘤作用。我们进一步证明，AC-CF增强的辅助抗肿瘤作用不仅通过下调MDR-1表达，还通过COX-2依赖性凋亡途径，包括下调COX-2和p-AKT以及上调PARP-1。总之，在本研究中，我们证明了一种将樟芝与中药材共发酵（AC-CF）的新策略，与传统方法（AC-FB或AC-SS）相比，该策略增强了其对人肝癌HepG2细胞的抗肿瘤作用。
