Li Xiaoli, Zou Kaili, Gou Jing, Du Qin, Li Dejuan, He Xiaoyan, Li Zhubo
College of Pharmaceutical Sciences, Southwest University, No. 2, Tiansheng Road, Beibei, Chongqing, 400716, People's Republic of China.
Med Oncol. 2015 Mar;32(3):72. doi: 10.1007/s12032-015-0527-9. Epub 2015 Feb 19.
The medical properties of baicalin have been well known for many years. However, the discovery that baicalin in the presence of metal ions is more effective than baicalin alone changed the course of drug research. The present study was designed to investigate the effect and possible mechanism of apoptosis induced by baicalin-copper in a human hepatoblastoma cancer cell line (HepG2) and in vivo. This study demonstrated that baicalin-copper suppresses the proliferation of HepG2 cells in a dose-dependent manner. Intraperitoneal injection of baicalin-copper resulted in a significant decrease in tumor growth in xenografts in nude mice. Acridine orange staining and flow cytometry analysis demonstrated that baicalin-copper induced apoptosis in HepG2 cells and caused cells to arrest in G2-M phase of the cell cycle. Furthermore, baicalin-copper treatment significantly increased the Bax/Bcl-2 ratio and p38 levels, as well as decreased the expression of caspase-3, p-PI3K, p-Akt and p-mTOR (P < 0.01). All of the evidences above indicate that baicalin-copper induces apoptosis in HepG2 cells by down-regulating the PI3K/Akt/mTOR signaling pathway.
多年来，黄芩苷的药用特性已广为人知。然而，金属离子存在下的黄芩苷比单独的黄芩苷更有效的这一发现改变了药物研究的进程。本研究旨在探讨黄芩苷 - 铜在人肝癌细胞系（HepG2）及体内诱导细胞凋亡的作用及可能机制。本研究表明，黄芩苷 - 铜以剂量依赖性方式抑制HepG2细胞的增殖。腹腔注射黄芩苷 - 铜导致裸鼠异种移植瘤的肿瘤生长显著降低。吖啶橙染色和流式细胞术分析表明，黄芩苷 - 铜诱导HepG2细胞凋亡并使细胞停滞在细胞周期的G2 - M期。此外，黄芩苷 - 铜处理显著增加了Bax/Bcl - 2比值和p38水平，同时降低了caspase - 3、p - PI3K、p - Akt和p - mTOR的表达（P < 0.01）。上述所有证据表明，黄芩苷 - 铜通过下调PI3K/Akt/mTOR信号通路诱导HepG2细胞凋亡。
