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

发布时间：2018-04-16 09:09

本文选题：骨肉瘤 + 细胞增殖　；参考：《山东医药》2017年16期

【摘要】：目的探讨雷帕霉素联合阿霉素对人骨肉瘤MG-63细胞(以下称骨肉瘤细胞)增殖的影响及其作用机制。方法取对数生长期骨肉瘤细胞,分别加入不同浓度的阿霉素(0.125、0.25、0.5、1.0、2.0 mg/L)和雷帕霉素(20、50、100 nmol/L)单独及联合作用,采用MTT法检测作用48 h的细胞增殖抑制率,并计算两药相互作用指数(CDI),评价两药相互作用性质。结果以100 nmol/L雷帕霉素与0.5 mg/L阿霉素联合作用后的细胞增殖抑制率最高,此时CDI0.7,两种药物表现为显著协同作用。将对数生长期的骨肉瘤细胞分为五组,阿霉素组、雷帕霉素组分别加入0.5 mg/L阿霉素、100 nmol/L雷帕霉素,联合用药组加入0.5 mg/L阿霉素和100 nmol/L雷帕霉素,DMSO溶媒组加入等量DMSO,空白对照组不予处理。采用MTT法检测各组细胞增殖能力,连续记录5天。采用Real-time PCR法检测各组处理48 h缺氧诱导因子1α(HIF-1α)、血管内皮生长因子(VEGF)、基质金属蛋白酶2(MMP-2)mRNA相对表达量。结果各组作用第1、2天细胞增殖能力比较差异均无统计学意义(P均0.05)。作用第3~5天,联合用药组细胞增殖能力均明显低于空白对照组、DMSO溶媒组、阿霉素组及雷帕霉素组(P均0.05)。联合用药组HIF-1α、VEGF、MMP-2 mRNA相对表达量均明显低于空白对照组、DMSO溶媒组、阿霉素组、雷帕霉素组(P均0.05)。结论雷帕霉素联合阿霉素可以协同抑制骨肉瘤细胞增殖;降低HIF-1α、VEGF、MMP-2表达可能是其作用机制。
[Abstract]:Objective to investigate the effect and mechanism of rapamycin combined with doxorubicin on proliferation of human osteosarcoma MG-63 cells.Methods Osteosarcoma cells in logarithmic phase were treated with different concentrations of doxorubicin (0.125) 0.25 ~ (0.5) (1.0 mg / L) and rapamycin (2050nmol / L) alone or in combination. The inhibitory rate of proliferation of osteosarcoma cells exposed to different concentrations of doxorubicin (0.125) and rapamycin (2050nmol / L) for 48 h was measured by MTT assay.The interaction index of two drugs was calculated and the interaction properties of two drugs were evaluated.Results the inhibition rate of cell proliferation was the highest after the combination of 100 nmol/L rapamycin and 0.5 mg/L doxorubicin, and CDI0.7The two drugs showed significant synergistic effect.The osteosarcoma cells in logarithmic phase were divided into five groups: adriamycin group and rapamycin group were treated with 0.5 mg/L doxorubicin and 100 nmol/L rapamycin, respectively.In combination group, doxorubicin for 0.5 mg/L and rapamycin for 100 nmol/L were added in the same amount of DMSO.The blank control group was not treated.The proliferative ability of each group was measured by MTT assay and recorded for 5 days.The relative expression of hypoxia inducible factor-1 伪 (HIF-1 伪), vascular endothelial growth factor (VEGF) and matrix metalloproteinase (2(MMP-2)mRNA) were detected by Real-time PCR assay.Results there was no significant difference in proliferative ability between the two groups on the 1st day (P < 0.05).On the 3rd day of treatment, the cell proliferation ability in the combination group was significantly lower than that in the DMSO solvent group, doxorubicin group and rapamycin group (P < 0.05).The relative expression of HIF-1 伪 VEGF MMP-2 mRNA in combination group was significantly lower than that in control group, adriamycin group and rapamycin group (P < 0.05).Conclusion rapamycin combined with doxorubicin can synergistically inhibit the proliferation of osteosarcoma cells, and the decrease of HIF-1 伪 -VEGF- MMP-2 expression may be its mechanism.
【作者单位】：新乡医学院第一附属医院;广西医科大学第一附属医院;
【基金】：广西自然科学基金资助项目(2012GXNSFAA05314;2014GXNSFAA118173) 广西高校科学技术研究项目(YB2014073)
【分类号】：R738.1

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