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目的:观察9-顺式维甲酸(9-cis retinoic acid,RA)联合细胞毒药物对MYCN扩增型神经母细胞瘤(neuroblastoma,NB)细胞的毒性及MYCN、MDR1表达的影响,为临床合理用药提供依据。方法:RA分别与长春新碱(VCR)、顺铂(CDDP)、足叶乙甙(VP16)、阿霉素(ADR)双药联合或单独作用IMR32细胞株24h后:(1)CCK-8法测定细胞生长抑制率;(2)流式细胞仪检测细胞凋亡率;(3)实时荧光定量PCR法检测MYCN、MDR1的mRNA表达。结果:(1)细胞生长抑制率:各双药组高于相应单药组(P<0.01)。(2)细胞凋亡率:双药组高于相应单药组(P<0.01),RA+CDDP高于其他双药组(P<0.05)。(3)MYCN表达:各双药组均低于相应单药组(P<0.05),RA+VCR低于其他双药组(P<0.05);MDR1表达:双药组高于相应单药组(P<0.05),RA+ADR高于其他双药组(P<0.01)。结论:RA联合细胞毒药物对NB生长抑制、凋亡及下调MYCN表达有协同作用,可上调MDR1表达,综合分析RA与VCR或CDDP的组合可能为临床联合用药提供较合理的选择。
OBJECTIVE: To observe the effect of 9-cis retinoic acid (RA) combined with cytotoxic drugs on the cytotoxicity of MYCN and the expression of MYCN and MDR1 in MYCN, Drugs provide the basis. Methods: IMR32 cells were treated with RA or VCR, CDDP, VP16 or ADR respectively for 24 hours: (1) CCK-8 (2) flow cytometry to detect apoptosis rate; (3) real-time fluorescence quantitative PCR detection MYCN, MDR1 mRNA expression. Results: (1) The rate of cell growth inhibition was higher in each two drug group than in the corresponding single drug group (P <0.01). (2) The rate of apoptosis was higher in double drug group than in corresponding single drug group (P <0.01), RA + CDDP was higher than other two drug groups (P <0.05). (3) The expression of MYCN in each group was lower than that in the corresponding single drug group (P <0.05), and RA + VCR was lower than that in other two drug groups (P <0.05). MDR1 expression was higher in the two drug groups than in the corresponding single drug group (P <0.05), RA + ADR was higher than other two groups (P <0.01). CONCLUSION: RA combined with cytotoxic drugs have synergistic effect on the growth inhibition, apoptosis and down-regulation of MYCN expression, and upregulate the expression of MDR1. The combination of RA and VCR or CDDP may provide a more reasonable alternative for clinical combination therapy.