Coadministration of Paclitaxel and Curcumin in Nanoemulsion Formulations To Overcome Multidrug Resistance in Tumor Cells
Coadministration of Paclitaxel and Curcumin in Nanoemulsion Formulations To Overcome Multidrug Resistance in Tumor Cells
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DOI：
10.1021/mp800240j
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发表时间：
2009-05-01
影响因子：
4.9
通讯作者：
Amiji, Mansoor
中科院分区：
文献类型：
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作者：
Ganta, Srinivas;Amiji, Mansoor
针对多种常规和新型化疗药物的多药耐药（MDR）的发展是有效的癌症治疗中的重大挑战。在过去的几年里，我们一直专注于多模式治疗策略，以克服肿瘤MDR，通过提高递送效率的肿瘤块和降低细胞凋亡阈值的细胞内信号转导机制的调制。在这项研究中，我们已经检查了紫杉醇（PTX）和姜黄素（CUR），一种核因子κ B（NF κ B）的抑制剂，以及一种有效的ABC转运蛋白的下调剂，在野生型SKOV 3和耐药SKOV 3（TR）人卵巢腺癌细胞联合给药后的治疗效果的增强。将PTX和CUR包封在含有亚麻籽油的纳米乳液制剂中。结果表明，包封的药物在SKOV 3和SKOV 3 TR细胞中均被有效地递送到细胞内。CUR给药显示抑制NF κ B B活性并下调耐药细胞中的P-糖蛋白表达。PTX和CUR联合治疗，特别是当以纳米乳液制剂给药时，通过促进凋亡反应在增强野生型和抗性细胞中的细胞毒性方面非常有效。总的来说，这种综合治疗策略在难治性疾病的临床管理中具有重要的前景，特别是在卵巢癌中。
Development of multidrug resistance (MDR) against a variety of conventional and novel chemotherapeutic agents is a significant challenge in effective cancer therapy. Over the last several years, we have focused on a multimodal therapeutic strategy to overcome tumor MDR by enhancing the delivery efficiency to the tumor mass and lowering the apoptotic threshold by modulation of the intracellular signaling mechanisms. In this study, we have examined augmentation of therapeutic efficacy upon coadministration of paclitaxel (PTX) and curcumin (CUR), an inhibitor of nuclear factor kappa B (NF kappa B) as well as a potent down-regulator of ABC transporters, in wild-type SKOV3 and drug resistant SKOV3(TR) human ovarian adenocarcinoma cells. PTX and CUR were encapsulated in flaxseed oil containing nanoemulsion formulations. The results showed that the encapsulated drugs were effectively delivered intracellular in both SKOV3 and SKOV3TR cells. CUR administration was shown to inhibit NF kappa B activity and down regulate P-glycoprotein expression in resistant cells. Combination PTX and CUR therapy, especially when administered in the nanoemulsion formulations, was very effective in enhancing the cytotoxicity in wild-type and resistant cells by promoting the apoptotic response. Overall, this cotherapy strategy has significant promise in the clinical management of refractory diseases, especially in ovarian cancer.