标题：Grape seed procyanidins induces apoptosis and inhibits proliferation of osteosarcomas cells in vitro
作者：Li, Yu; Sun, Yujie; Si, Meng
作者机构：[Li, Yu] Yantaishan Hosp, Dept Traumat 4, 91 Jiefang Rd, Zhifu Dist 264001, Yantai, Peoples R China.; [Sun, Yujie] Qingdao Univ, Affiliated Yantai Y 更多
通讯作者地址：[Si, M]Shandong Univ, Qilu Hosp, Dept Orthopaed Surg, 107 Wenhua West Rd, Jinan 250012, Shandong, Peoples R China.
来源：INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE
关键词：Grape seed procyanidins; osteosarcoma; viability; apoptosis
摘要：Objective: Grape seed procyanidins (GSPs) have attracted more attention for its anti-tumor activity. In this study, we aimed to explore the effect of GSPs on the growth of osteosarcoma cells and the potential mechanisms. Methods: Human MG63 osteosarcoma cells were treated with different concentrations of GSPs (0, 10, 50, 100 mu g/ml) to find an optimal stimulating dose. MTT and TUNEL assay were performed for measurement of cell variability and apoptosis. Based on the result of dose-dependent study, cells were treated with GSPs (0 and 100 mu g/ ml). As Bax, Bcl-2 and caspase family exert key roles in regulation of apoptosis, and Cdks and cyclins play a critical role in the regulation of cell cycle progression, we performed western blot assay for measurement of their expressions stimulated by GSPs. ERK1/2, PI3K and Akt were also detected by western blot as the important signallings mediating cell proliferation and survival. In addtion, RT-PCR was used to obtain the mRNA levels of caspase-3 and caspase-8. Results: GSPs inhibited cell variability and induced apoptosis in a dose-dependent manner. GSPs downregulated anti-apoptotic factor bcl-2 and bcl-xl expression, up-regulated pro-apoptotic factor Bax expression and increased the activity of caspase-3 and caspase-8. GSPs also significantly decreased the expression of Cdk2, Cdk4, cyclins D1 and Cyclins D2. In addition, GSPs suppressed the activation of ERK1/2 and PI3K/Akt signaling pathway. Conclusion: GSPs inhibited cell variability and induced apoptosis which might be regulated by ERK1/2 and PI3K/Akt signaling pathway. GSPs might represent a promising and effective therapeutic strategy in osteosarcoma management.