CDK抑制剂NSC649890联合顺铂对人骨肉瘤细胞U2-OS的抑制作用

发布时间：2018-02-03 16:15

  本文关键词： 人骨肉瘤U-OS细胞 CDK抑制剂 顺铂 细胞增殖 细胞凋亡　出处：《中国矫形外科杂志》2017年01期 　论文类型：期刊论文

【摘要】：[目的]探讨CDK抑制剂NSC 649890联合顺铂对人骨肉瘤U2-OS细胞抑制作用及可能的机制。[方法]MTT法检测分别采用50、100、200、400、800 nmol/L的NSC 649890 2、4、6、8、10μg/ml顺铂、50 nmol的NSC649890联合2μg/ml顺铂、300nmol的NSC 649890联合6μg/ml顺铂培养48 h后细胞增殖情况,金氏q值评价联合用药效应;流式细胞仪、Western blotting检测分别采用300 nmol/L的NSC 649890、6μg/ml顺铂及二者联合培养48 h后细胞凋亡及凋亡通路相关蛋白表达情况,以上实验均以单纯U2-OS细胞作为对照组。[结果]U2-OS细胞经不同浓度顺铂、NSC 649890单独处理48 h后,细胞抑制率随两种药物浓度增加而显著升高,比较差异均有统计学意义(P0.05)。在联合用药组中,顺铂与NSC 649890联合浓度(2μg/ml+50 nmol/L)组两药为协同作用,(6μg/ml+300nmol/L)组两药为相加作用。流式细胞仪检测显示,顺铂组、NSC 649890组及联合组细胞凋亡率显著高于对照组(P0.05)。Western blotting检测结果显示,与对照组相比,顺铂和NSC 649890单独作用后均可下调Bcl-2蛋白、procaspase-3蛋白的表达水平及上调Bax蛋白的表达水平,差异均有统计学意义(P0.05),而两者联合作用时效果更加显著(P0.05)。[结论]NSC 649890能增强顺铂对人骨肉瘤U2-OS细胞的抑制作用。
[Abstract]:[Objective] to investigate the inhibitory effect of CDK inhibitor NSC 649890 combined with cisplatin on human osteosarcoma U2-OS cells and its possible mechanism. [Methods] MTT method was used to detect cisplatin 10 渭 g / ml of 50,100,200,400,800 nmol/L NSC (649890 2G / ml). The proliferation of 50 nmol NSC649890 combined with 2 渭 g / ml Cisplatin 300nmol NSC649890 and 6 渭 g / ml Cisplatin for 48 h was observed. Kim's Q value was used to evaluate the effect of combined medication. Western blotting was used to detect NSC 649890 of 300 nmol/L by flow cytometry. 6 渭 g / ml cisplatin and co-cultured with cisplatin and both for 48 h, apoptosis and apoptosis-pathway related protein expression, U2-OS cells were used as control group. [Results: the inhibition rate of U2-OS cells increased significantly with the increase of the concentration of two drugs after 48 hours of treatment with different concentrations of cisplatin or NSC 649890 alone. The difference was statistically significant in the combination group. The synergistic effect of cisplatin and NSC 649890 was observed in 2 渭 g / ml 50 nmol / L group. 6 渭 g / ml 300nmol / L) group was additive. Flow cytometry showed that the cisplatin group was treated with Cisplatin. The rate of apoptosis in NSC 649890 group and combined group was significantly higher than that in control group (P 0.05). Western blotting assay showed that the apoptosis rate was significantly higher than that in control group. Both cisplatin and NSC 649890 could down-regulate the expression of Bcl-2 protein procaspase-3 and up-regulate the expression of Bax protein. The difference was statistically significant (P 0.05), and the effect of combined action was more significant than that of P0.05 (P 0.05). [Conclusion NSC 649890 can enhance the inhibitory effect of cisplatin on human osteosarcoma U2-OS cells.
【作者单位】： 南昌大学第一附属医院骨科;
【基金】：江西省卫生厅科技计划资助项目(编号:20091059),江西省卫生厅中医药科研课题(编号:2012A136) 江西省自然基金资助项目(编号:2010JX02603;20132BAB205081)
【分类号】：R738.1
【正文快照】： 骨肉瘤是一种主要发病人群为青少年的原发性恶性肿瘤,其强侵袭性常导致患者早期即出现肿瘤细胞远处转移。目前应对骨肉瘤的临床治疗主要以化疗-手术-化疗为主[1-2]。顺铂是骨肉瘤化疗的常见药物之一,但临床证实骨肉瘤细胞对顺铂易产生耐药性[3-4]。小分子细胞周期素依赖性蛋白，

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