Mangiferin enhances the sensitivity of human multiple myeloma cells to anticancer drugs through suppression of the nuclear factor κB pathway
Mangiferin enhances the sensitivity of human multiple myeloma cells to anticancer drugs through suppression of the nuclear factor κB pathway
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DOI：
10.3892/ijo.2016.3470
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发表时间：
2016-06-01
影响因子：
5.2
通讯作者：
Nishida, Shozo
中科院分区：
文献类型：
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作者：
Takeda, Tomoya;Tsubaki, Masanobu;Nishida, Shozo
多发性骨髓瘤(MM)仍然是一种无法治愈的血液系统恶性肿瘤，尽管采用了各种治疗方法，但5年生存率仍高达35%。核因子-kappaB(NF-kappa B)通路在MM的发病机制中起着至关重要的作用，因此抑制NF-kappa B通路是治疗MM的一个潜在靶点。在以前的研究中，我们发现芒果苷抑制了NF-kappa B的核转位。在这项研究中，我们研究了芒果苷与传统抗癌药物在MM细胞系中的联合作用。我们发现，芒果苷和一种抗癌药物联合使用时，与单独使用两种药物相比，MM细胞系的存活率降低。芒果苷与抗癌药物联合作用后细胞存活率下降的原因是通过抑制核因子-kappa B通路，增加P53和NoxA的表达，降低XIAP、Survivin和Bclxl蛋白的表达。此外，联合作用可诱导细胞凋亡，激活caspase-3，并使细胞积聚在细胞周期的亚G1期。我们的研究结果表明，芒果苷与抗癌药物联合治疗MM有可能成为一种新的治疗方法。
Multiple myeloma (MM) is still an incurable hematological malignancy with a 5-year survival rate of 35%, despite the use of various treatment options. The nuclear factor kappa B (NF-kappa B) pathway plays a crucial role in the pathogenesis of MM. Thus, inhibition of the NF-kappa B pathway is a potential target for the treatment of MM. In a previous study, we showed that mangiferin suppressed the nuclear translocation of NF-kappa B. However, the treatment of MM involves a combination of two or three drugs. In this study, we examined the effect of the combination of mangiferin and conventional anticancer drugs in an MM cell line. We showed that the combination of mangiferin and an anticancer drug decreased the viability of MM cell lines in comparison with each drug used separately. The decrease in the combination of mangiferin and an anticancer drug induced cell viability was attributed to increase the expression of p53 and Noxa and decreases the expression of XIAP, survivin, and Bcl-xL proteins via inhibition of NF-kappa B pathway. In addition, the combination treatment caused the induction of apoptosis, activation of caspase-3 and the accumulation of the cells in the sub-G1 phase of the cell cycle. Our findings suggest that the combination of mangiferin and an anticancer drug could be used as a new regime for the treatment of MM.