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首页> 外文期刊>Drug Design, Development and Therapy >Inactivation of nuclear factor κB by MIP-based drug combinations augments cell death of breast cancer cells
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Inactivation of nuclear factor κB by MIP-based drug combinations augments cell death of breast cancer cells

机译：基于MIP的药物组合对核因子κB的灭活增加了乳腺癌细胞的细胞死亡

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Background: Drug combination therapy to treat cancer is a strategic approach to increase successful treatment rate. Optimizing combination regimens is vital to increase therapeutic efficacy with minimal side effects. Materials and methods: In the present study, we evaluated the in vitro cytotoxicity of double and triple combinations consisting of 1'S-1'-acetoxychavicol acetate (ACA), Mycobacterium indicus pranii (MIP) and cisplatin (CDDP) against 14 various human cancer cell lines to address the need for more effective therapy. Our data show synergistic effects in MCF-7 cells treated with MIP:ACA, MIP:CDDP and MIP:ACA:CDDP combinations. The type of interaction between MIP, ACA and CDDP was evaluated based on combination index being <0.8 for synergistic effect. Identifying the mechanism of cell death based on previous studies involved intrinsic apoptosis and nuclear factor kappa B (NF-κB) and tested in Western blot analysis. Inactivation of NF-κB was confirmed by p65 and IκBα, while intrinsic apoptosis pathway activation was confirmed by caspase-9 and Apaf-1 expression Results: All combinations confirmed intrinsic apoptosis activation and NF-κB inactivation. Conclusion: Double and triple combination regimens that target induction of the same death mechanism with reduced dosage of each drug could potentially be clinically beneficial in reducing dose-related toxicities.
机译：背景：药物联合治疗癌症是提高成功治疗率的战略方法。优化组合方案对于以最小的副作用提高治疗效果至关重要。材料和方法：在本研究中，我们评估了由1'S-1'-醋酸乙酰氧基查韦醇（ACA），印度分枝杆菌（MIP）和顺铂（CDDP）组成的双重和三重组合对14种人类癌细胞的体外细胞毒性线，以解决更有效的治疗需求。我们的数据显示了在用MIP：ACA，MIP：CDDP和MIP：ACA：CDDP组合治疗的MCF-7细胞中的协同效应。 MIP，ACA和CDDP之间的相互作用类型基于协同作用的联合指数<0.8进行了评估。根据先前的研究鉴定细胞死亡的机制涉及内在凋亡和核因子κB（NF-κB），并在蛋白质印迹分析中进行了测试。 p65和IκBα证实了NF-κB的失活，而caspase-9和Apaf-1的表达证实了内在的凋亡途径的激活。结果：所有组合均证实了内在的凋亡激活和NF-κB的失活。结论：以减少每种药物的剂量为目标的相同死亡机制的诱导的双重和三次组合方案可能在减少剂量相关毒性方面具有临床益处。

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