Laboratory of Molecular Pharmacology, School of Pharmacy, Yantai University, No. 30, Qing Quan Lu, Lai Shan Qu, 264005, Yantai, Shandong Province, China.
Cytotechnology. 2010 Aug;62(4):341-8. doi: 10.1007/s10616-009-9240-x. Epub 2009 Dec 6.
The purpose of this study is to investigate the effects of berbamine (BER), a naturally occurring small-molecule compound from Traditional Chinese Medicine (TCM) Berberis amurensis, on the growth and migration of human lung cancer A549 cell line. This cell line is the non-small cell lung cancer (NSCLC) which constitutes 80% of lung cancer cases and remains an aggressive lung cancer associated with a poor patient survival. Our present results have shown that BER significantly suppressed the in vitro and ex vivo growth of A549 cells in dose- and time-dependent manners. Furthermore, Western blot analysis confirmed that BER dose-dependently down-regulated the expression of anti-apoptotic protein Bcl-2 and up-regulated the level of pro-apoptotic protein Bax, eventually leading the reduction of Bcl-2/Bax protein ratio in A549 cells. In addition, BER significantly inhibited the A549 cell migration at the low concentrations without restraining the cell growth. More importantly, BER significantly enhanced the anticancer activity of anticancer agents such as trichostatin A (the histone deacetylase inhibitor) and celecoxib (the inhibitor of cyclooxygenase-2) by strongly reducing the viability and/or the Bcl-2/Bax protein ratio in A549 cells. Our findings suggest that BER may have the wide therapeutic and/or adjuvant therapeutic application in the treatment of human NSCLC.
本研究旨在探讨小檗胺（BER）对人肺癌 A549 细胞系生长和迁移的影响。该细胞系为非小细胞肺癌（NSCLC），占肺癌病例的 80%，仍然是一种侵袭性肺癌，患者生存率较差。我们目前的结果表明，BER 以剂量和时间依赖的方式显著抑制 A549 细胞的体外和体内生长。此外，Western blot 分析证实，BER 剂量依赖性地下调抗凋亡蛋白 Bcl-2 的表达，并上调促凋亡蛋白 Bax 的水平，最终导致 A549 细胞中 Bcl-2/Bax 蛋白比值降低。此外，BER 显著抑制 A549 细胞在低浓度时的迁移，而不抑制细胞生长。更重要的是，BER 显著增强了抗癌药物如曲古抑菌素 A（组蛋白去乙酰化酶抑制剂）和塞来昔布（环氧化酶-2 抑制剂）的抗癌活性，强烈降低了 A549 细胞的活力和/或 Bcl-2/Bax 蛋白比值。我们的研究结果表明，BER 可能在治疗人类 NSCLC 方面具有广泛的治疗和/或辅助治疗应用。
