State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
Toxicol Appl Pharmacol. 2012 Mar 15;259(3):387-94. doi: 10.1016/j.taap.2012.01.019. Epub 2012 Jan 30.
Oroxylin A, a naturally occurring monoflavonoid extracted from Scutellariae radix, shows effective anticancer activities and low toxicities both in vivo and in vitro in previous studies. In this study, we investigated whether the CAM-DR model of HepG2 cells showed resistance to cytotoxic agents compared with normally cultured HepG2 cells. Furthermore, after the treatment of Paclitaxel, less inhibitory effects and decreased apoptosis rate were detected in the model. Data also revealed increased expression of Integrinβ1 might be responsible for the resistance ability. Moreover, Integrinβ1-siRNA-transfected CAM-DR HepG2 cells exhibited more inhibitory effects and higher levels of apoptosis than the non-transfected CAM-DR cells. The data corroborated that Integrinβ1 played a significant role in CAM-DR. After the treatment of weakly-toxic concentrations of Oroxylin A, the apoptosis induced by Paclitaxel in the CAM-DR model increased dramatically. Western blot assay revealed Oroxylin A markedly down-regulated the expression of Integrinβ1 and the activity of related pathway. As a conclusion, Oroxylin A can reverse the resistance of CAM-DR via inhibition of Integrinβ1 and its related pathway. Oroxylin A may be a potential candidate of a CAM-DR reversal agent.
在之前的研究中，从黄芩中提取的天然单黄酮氧芴 A 在体内和体外均显示出有效的抗癌活性和低毒性。本研究探讨了与正常培养的 HepG2 细胞相比，CAM-DR 型 HepG2 细胞对细胞毒剂是否表现出耐药性。此外，在紫杉醇处理后，模型中检测到抑制作用降低和凋亡率降低。数据还表明，整合素β1 的表达增加可能是耐药能力的原因。此外，与非转染的 CAM-DR 细胞相比，转染 Integrinβ1-siRNA 的 CAM-DR HepG2 细胞表现出更强的抑制作用和更高水平的凋亡。数据证实 Integrinβ1 在 CAM-DR 中起重要作用。用低毒性浓度的氧芴 A 处理后，CAM-DR 模型中紫杉醇诱导的细胞凋亡显著增加。Western blot 分析表明，氧芴 A 明显下调了整合素β1 的表达及其相关途径的活性。总之，氧芴 A 可以通过抑制整合素β1 及其相关途径来逆转 CAM-DR 的耐药性。氧芴 A 可能是一种潜在的 CAM-DR 逆转剂候选药物。
