Liu Zeng, Zhu Yuan-Yuan, Li Zhao-Yuan, Ning Si-Qing
Department of Nuclear Medicine, Central Hospital of Xiangyang, Xiangyang, Hubei 441021, P.R. China.
No. 1 Hospital of Xiangyang, Xiangyang, Hubei 441000, P.R. China.
Oncol Lett. 2016 Nov;12(5):3944-3948. doi: 10.3892/ol.2016.5192. Epub 2016 Sep 26.
The aim of the present study was to evaluate the efficacy of paclitaxel combined with curcumin (CUR) against drug resistance in ovarian cancer cells. PLGA-phospholipid-PEG nanoparticles were prepared using the nano precipitation method. The size and morphology of the nanoparticles were determined using a transmission electron microscope and particle size analyzer. The encapsulation efficiency of nanoparticles was determined using the ultrafiltration centrifugation method. The dialysis method was used to study the release of PLGA-phospholipid-PEG nanoparticles. ADM was used to induce the A2780 cell line (human ovarian cancer cell line) to establish the model of the multidrug-resistant (MDR) cell line, and the protein activity of P-glycoprotein (P-gp) in the A2780 cell line and A2780/ADM resistant cell line was determined using western blot analysis. The results showed that, the prepared nanoparticles were uniform in size, with a size of approximately 100 nm, and round in shape. Additionally, the nanoparticles had a more gentle and slow release than the free drug release. The results of the protein trace printing experiment showed that the P-gp content of the drug-resistant cell line was significantly reduced by the CUR nanoparticles. In conclusion, PLGA-phospholipid nanoparticles containing taxol and CUR have improved solubility and stability together with a slow release effect. In addition, CUR was able to overcome the MDR of tumor cells by elevating the paclitaxel concentration in the tumor cells to improve the antitumor activity of this combination.
本研究的目的是评估紫杉醇联合姜黄素(CUR)对卵巢癌细胞耐药性的疗效。采用纳米沉淀法制备聚乳酸-羟基乙酸共聚物-磷脂-聚乙二醇纳米粒。使用透射电子显微镜和粒度分析仪测定纳米粒的大小和形态。采用超滤离心法测定纳米粒的包封率。采用透析法研究聚乳酸-羟基乙酸共聚物-磷脂-聚乙二醇纳米粒的释放情况。使用阿霉素(ADM)诱导A2780细胞系(人卵巢癌细胞系)建立多药耐药(MDR)细胞系模型,并通过蛋白质免疫印迹分析测定A2780细胞系和A2780/ADM耐药细胞系中P-糖蛋白(P-gp)的蛋白活性。结果表明,所制备的纳米粒大小均匀,尺寸约为100 nm,呈圆形。此外,纳米粒的释放比游离药物释放更温和、更缓慢。蛋白质印迹实验结果表明,CUR纳米粒可显著降低耐药细胞系中的P-gp含量。总之,含有紫杉醇和CUR的聚乳酸-羟基乙酸共聚物-磷脂纳米粒具有改善的溶解性和稳定性以及缓释效果。此外,CUR能够通过提高肿瘤细胞中的紫杉醇浓度来克服肿瘤细胞的多药耐药性,从而提高该组合的抗肿瘤活性。