山东医药2017,Vol.57Issue(16):8-11,4.DOI:10.3969/j.issn.1002-266X.2017.16.003
雷帕霉素联合阿霉素对人骨肉瘤MG-63细胞增殖的影响及其机制
Effects of Rapamycin and Adriamycin on proliferation of osteosarcoma MG-63 cells
摘要
Abstract
Objective To investigate the effects of Rapamycin (RAPA) and Adriamycin (ADM) on proliferation of osteosarcoma MG-63 cells and their mechanisms.Methods Human osteosarcoma MG-63 cells in logarithmic growth phase was treated with ADM solution of different concentrations (0.125, 0.25, 0.5, 1.0, 2.0 mg/L) and RAPA solution of different concentrations (20, 50, 100 nmol/L) alone or in combination.Then the cell inhibition rate was determined by MTT after 48 hours, and Coefficient of drug interaction (CDI) was calculated to evaluate the nature of the interaction between the two drugs.The cell inhibition rate was the highest when MG-63 cells were treated with 100 nmol/L RAPA combined with 0.5 mg/L ADM.At this moment, CDI was less than 0.7 and the two drugs showed a significant synergistic effect.According to the optimal combination concentration, we randomly divided MG-63 cells in logarithmic growth phase into five groups: ADM group (treated with 0.5 mg/L ADM), RAPA group (treated with 100 nmol/L RAPA), the combination group (treated with 0.5 mg/L ADM and 100 nmol/L RAPA), DMSO solvent group (treated with the same concentration of DMSO) and the blank control group (without any treatment).The cell proliferation ability was detected by MTT for 5 days.The expression levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and matrix metalloproteinase 2 (MMP-2) mRNA were analyzed by real-time PCR at 48 h.Results There was no significant difference in cell proliferation ability among these groups on day 1 and 2 (all P>0.05).The cell proliferation ability of the combination group was lower than those of the blank control group, DMSO solvent group, ADM group and RAPA group on day 3-5 (all P<0.05).The relative expression of HIF-1α, VEGF and MMP-2 mRNA in the combination group was significantly lower than that in the blank control group, DMSO solvent group, ADM group and RAPA group (all P<0.05).Conclusion RAPA combined with ADM may synergistically inhibit the proliferation of human osteosarcoma MG-63 cells by decreasing the expression of HIF-1α, VEGF, MMP-2 mRNA.关键词
骨肉瘤/细胞增殖/雷帕霉素/阿霉素/药物敏感性Key words
osteosarcoma/cell proliferation/Rapamycin/Adriamycin/drug sensitivity分类
医药卫生引用本文复制引用
崔明星,詹新立,刘冲,邓黎,熊春翔,刘会江..雷帕霉素联合阿霉素对人骨肉瘤MG-63细胞增殖的影响及其机制[J].山东医药,2017,57(16):8-11,4.基金项目
广西自然科学基金资助项目(2012GXNSFAA05314、2014GXNSFAA118173) (2012GXNSFAA05314、2014GXNSFAA118173)
广西高校科学技术研究项目(YB2014073). (YB2014073)