Shang Kuang-Ming, Su Tzu-Hsuan, Lee Wai Leng, Hsiao Wen-Wei, Chiou Ching-Yi, Ho Bing-Ying, Wang Sheng-Yang, Shyur Lie-Fen
Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
School of Science, Monash University Sunway Campus, Selangor, Malaysia.
Phytomedicine. 2017 Jan 15;24:39-48. doi: 10.1016/j.phymed.2016.11.006. Epub 2016 Nov 8.
Tamoxifen, an anti-oestrogenic drug for estrogen receptor positive (ER+) breast cancer, was observed to stimulate tumor growth or drug resistance in patients. Antrodia cinnamomea (AC), a precious medicinal fungus has been traditionally used as a folk remedy for cancers in Asian countries. The objective of this study was to investigate the bioefficacy and the underlying molecular mechanisms of the AC fruiting bodies extracts (AC-3E) against human ER+ T47D breast cancer cells, and compare the effect with that of tamoxifen.
Cell proliferation, migration, TUNEL assay, western blotting, time-lapse confocal microscopy analyses, chorioallantoic membrane assay, and a xenograft BALB/c nude mouse system were used in this study. Chemical fingerprinting of AC-3E was established using LC-MS.
AC-3E attenuated T47D breast cancer cell activity by deregulating the PI3K/Akt/mTOR signaling pathway and key cell-cycle mediators, and inducing apoptosis. AC-3E also effectively inhibited tube-like structures of endothelial cells, blood vessel branching and microvessel formation ex vivo and in vivo. Significant preventive and therapeutic effects against T47D mammary tumor growth of AC-3E was observed comparable or superior to tamoxifen treatment in xenograft BALB/c nude mice. Dehydroeburicoic acid (2) was characterized as the main chemical constituent in AC-3E against breast cancer.
This study suggests that AC-3E extracts can be employed as a double-barreled approach to treat human ER+ breast cancer by attacking both cancer cells and tumor-associated blood vessel cells.
他莫昔芬是一种用于雌激素受体阳性（ER+）乳腺癌的抗雌激素药物，但在患者中观察到它会刺激肿瘤生长或导致耐药。樟芝（AC）是一种珍贵的药用真菌，在亚洲国家传统上被用作治疗癌症的民间药物。本研究的目的是探讨樟芝子实体提取物（AC-3E）对人ER+ T47D乳腺癌细胞的生物功效及其潜在分子机制，并与他莫昔芬的效果进行比较。
本研究采用细胞增殖、迁移、TUNEL检测、蛋白质印迹法、延时共聚焦显微镜分析、鸡胚绒毛尿囊膜试验和异种移植BALB/c裸鼠系统。使用液相色谱-质谱联用技术建立AC-3E的化学指纹图谱。
AC-3E通过调节PI3K/Akt/mTOR信号通路和关键细胞周期调节因子，诱导细胞凋亡，从而减弱T47D乳腺癌细胞的活性。AC-3E还能在体外和体内有效抑制内皮细胞的管状结构、血管分支和微血管形成。在异种移植BALB/c裸鼠中，观察到AC-3E对T47D乳腺肿瘤生长具有显著的预防和治疗作用，其效果与他莫昔芬相当或更优。脱氢齿孔酸（2）被鉴定为AC-3E中对抗乳腺癌的主要化学成分。
本研究表明，AC-3E提取物可通过同时攻击癌细胞和肿瘤相关血管细胞，作为一种双管齐下的方法来治疗人ER+乳腺癌。
