白藜芦醇对维甲酸治疗髓母细胞瘤的增敏作用及机制研究

Sensitizing Effect and Mechanism of Resveratrol on Retinoic Acid Treatment of Medulloblastoma

目的:明确白藜芦醇(Res)增强髓母细胞瘤(MB)细胞对全反式维甲酸(RA)敏感性的效果。方法:选取MB细胞系(Med-3、UW228-2、UW228-3)并构建裸鼠原位瘤模型,通过离体和在体研究观察联合给药对MB细胞的凋亡、增殖及相关信号通路的影响。结果:联合给药能够明显抑制MB细胞增殖活性,有效减少了肿瘤细胞数量;通过联合给药都能够上调肿瘤细胞内的CRABP2及其胞内RA受体RAR/RXR的表达,进而上调Bax和c-caspase3,下调Bcl2的表达。结论:Res通过激活CRABP2通路增强MB对RA敏感性,进而激活凋亡信号通路,诱导肿瘤细胞发生凋亡。

Objective:The aim is well established that resveratrol(Res)is able to enhance the sensitivity of medulloblastoma(MB)to all trans retinoic acid(RA).Methods:MB cell lines(Med-3,UW228-2,UW228-3)were cultured and orthotopic tumor models in nude mice were constructed,apoptosis,proliferation,and related signaling pathways in MB cells treated with Res plus RA were assessed by ex vivo and in vivo studies.Results:Combined administration could significantly inhibit the proliferation of MB cells and effectively reduce the number of tumor cells;the combined administration also upregulated the expression of CRABP2 and RA intracellular receptor RAR/RXR in tumor cells,upregulated Bax and c-caspase3,and downregulated the level of Bcl2.Conclusion:Res induces apoptosis of tumor cells through enhancing the sensitivity of MB to RA by activating CRABP2 pathway.