摘要
研究发现双膦酸盐(Bisphosphonates,BPs)类药物能抑制多种癌细胞系的生长。实验选用双膦酸盐类药物伊班磷酸钠(ibandronate,IB)和CP(化学名称为[2-(6-氨基-嘌呤-9-基)-1-羟基-膦酰乙基]膦酸,为河北医科大学药学院研制的新药)作用于体外培养的人胃癌细胞株SGC-7901,用噻唑氮蓝(MTT)比色实验、流式细胞术、免疫细胞化学染色、Western blot等方法研究分析双膦酸盐类药物对体外培养的人胃癌细胞株细胞增殖、细胞周期和细胞调亡的影响以及IL-6、p-STAT-3蛋白表达的影响。结果发现:BPs药物可抑制人胃癌细胞SGC-7901的增殖,CP的抑制作用强于IB。流式细胞术显示两种药物均可诱导SGC-7901细胞凋亡;BPs可以将细胞阻滞于S期,且有明显的量效和时效关系,CP的阻滞作用效果强于IB。免疫细胞化学染色和Western blot结果显示随着BPs作用时间延长,IL-6、p-STAT-3蛋白表达量逐渐降低,CP组作用强于IB组。提示BPs药物抗肿瘤作用机制可通过影响IL-6使STAT-3蛋白活化受抑制,以维护信号传导及转录活化因子的稳定,进而影响肿瘤细胞的增殖、凋亡,从而阻断肿瘤的发生。
Recent studies showed that many cancer cell lines could be inhibited by BPs. We used the ibandronate （IB） and CP on the human gastric adenocarcinoma cell line （SGC-7901） to further explore the mechanism. The methods of MTT, cytometric analysis, immunocytochemical staining and Western blot were employed to evaluate the influence of BPs on the proliferation, apoptosis and cycle of tumor cells and the expression of IL-6, p- STAT-3 protein in human gastric adenocarcinoma cell line （SGC-7901）. The result showed that SGC-7901 cell proliferation could be significantly inhibited by BPs, and the effect of CP was more significant than that of IB. FCM suggested that BPs stimulated apoptosis of SGC-7901 cells and inhibited cells on S phase, while S fraction cells increased in treated groups in a dose and time-dependent manner, the effect of CP was more significant than that of IB. The result of immunocytochemicai staining and Western blot showed that the relative content of IL-6 protein and p-STAT-3 protein in BPs treated group was lower than that in the control group; the effect of CP was more significant than IB. The anti-tumor mechanism of BPs was protecting the stabilization of signal transducer and activator of transcription, then affecting the proliferation and apoptosis of cancer cells by down-regulate protein expression of IL-6 and p-STAT-3.
出处
《中国细胞生物学学报》
CAS
CSCD
2010年第4期606-612,共7页
Chinese Journal of Cell Biology
