a The Central People's Hospital of Siping City , Siping , Jilin , China.
Artif Cells Nanomed Biotechnol. 2018;46(sup2):904-911. doi: 10.1080/21691401.2018.1472101. Epub 2018 May 14.
Combined administration regimens are commonly used in cancer therapy to reduce cell toxicity and drug resistance. In this study, we use solid lipid nanoparticles (SLNs) as drug carriers and sought to investigate the effect of combined administration of paclitaxel (PTX) and tanespimycin (17-AAG) in gastric cancer. The SLNs loaded with paclitaxel and tanespimycin were prepared using the solvent injection method. The effect of encapsulated SLNs on cell viability and colony formation were measured in three human gastric cell lines. Cell apoptosis assay was carried out in MKN45 cells and xenograft model was used to investigate the effect of encapsulated SLNs in vitro and in vivo. The expression levels of proteins involved in oxidative stress and apoptosis were measured by western blotting analysis. The encapsulated SLNs reduced cell viabilities and colony formation in gastric cell lines. These SLNs could also induce apoptosis in MKN45 cells, inhibit growth of xenograft and influence the protein levels of Hsp90, MnSOD, Cleaved caspase 3 and Cleaved PARP. The effect of encapsulated SLNs exceeded that of single treatment of PTX or 17-AAG. The combination administration of PTX or 17-AAG resulted in a synergetic anti-cancer effect, probably via an increased oxidative stress and apoptosis levels.
联合给药方案常用于癌症治疗，以降低细胞毒性和耐药性。在这项研究中，我们使用固体脂质纳米粒（SLNs）作为药物载体，并研究了紫杉醇（PTX）和坦西普尼（17-AAG）联合给药对胃癌的影响。采用溶剂注入法制备载有紫杉醇和坦西普尼的 SLNs。在三种人胃细胞系中测量载药 SLNs 对细胞活力和集落形成的影响。在 MKN45 细胞中进行细胞凋亡测定，并使用异种移植模型在体外和体内研究载药 SLNs 的作用。通过 Western blot 分析测量与氧化应激和细胞凋亡相关的蛋白表达水平。载药 SLNs 降低了胃细胞系的细胞活力和集落形成。这些 SLNs 还可以诱导 MKN45 细胞凋亡，抑制异种移植的生长，并影响 Hsp90、MnSOD、Cleaved caspase 3 和 Cleaved PARP 的蛋白水平。载药 SLNs 的效果超过了 PTX 或 17-AAG 单一治疗的效果。PTX 或 17-AAG 的联合给药产生协同抗癌作用，可能通过增加氧化应激和细胞凋亡水平实现。
