Department of Chemistry, Division of Biochemistry, Faculty of Science, Tanta University, Tanta, Egypt.
Department of Medical Biophysics, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Anticancer Agents Med Chem. 2020;20(13):1582-1591. doi: 10.2174/1871520620666200504071530.
Although the anticancer potentials of water-insoluble drugs are improved by nanoformulation, other intervening factors may contribute in the drug efficacy. This work was designated to explore the effect of paclitaxel-loaded Poly(Lactic-co-Glycolic Acid) (PLGA) nanoparticles on the viability of cancer cells, the expression of Taxol Resistance gene I (TXR1) and paclitaxel metabolizing genes.
Paclitaxel loaded PLGA Nanoparticles (PTX-NPs) were prepared, physically characterized and used in the treatment of breast adenocarcinoma cells (MCF-7) and hepatoma cells (HepG2). Cells viability and apoptosis were investigated. In parallel, RNA was isolated, reverse transcribed and used to monitor the expression levels of TXR1, CYP 3A4 and CYP2C8 genes.
PTX-NPs were characterized by transmission electron microscopy to be of a nano-size sphere-like shape. FTIR analysis revealed good coupling between PTX and PLGA. The encapsulation efficiency was 99% and the drug release demonstrated a progressive releasing phase followed by slower and sustained releasing phases. Although HepG2 cells demonstrated more resistance to PTX than MCF-7 cells, both cell types were more responsive to PTX-NPS compared to PTX. The IC50 values decreased from 19.3 to 6.7 in breast cancer cells and from 42.5 to 13.1μg/ml in hepatoma cells. The apoptosis was the key mechanism in both cells, where at least 44% of cells underwent apoptosis. The expression of TXR1 decreased when either cells were treated with PTX-NPs, respectively, meanwhile the expressions of CYP3A4 and CYP2C8 were increased.
Taken together, this in vitro study reports the associations between the enhanced responsiveness of MCF-7 and HepG2 cells to PLGA-loaded paclitaxel nanoparticles and the accompanying decrease in the cells resistance to the PTX and its enhanced metabolism.
虽然纳米制剂可以提高水不溶性药物的抗癌潜力，但其他干预因素也可能对药物疗效有贡献。本研究旨在探讨紫杉醇负载聚乳酸-羟基乙酸共聚物（PLGA）纳米粒对癌细胞活力、紫杉醇耐药基因 I（TXR1）和紫杉醇代谢基因表达的影响。
制备紫杉醇负载 PLGA 纳米粒（PTX-NPs），并对其进行物理特性表征，然后用于治疗乳腺腺癌细胞（MCF-7）和肝癌细胞（HepG2）。检测细胞活力和细胞凋亡。同时，提取 RNA 并逆转录，用于监测 TXR1、CYP3A4 和 CYP2C8 基因的表达水平。
透射电镜显示 PTX-NPs 为纳米级球形。傅里叶变换红外光谱分析显示 PTX 与 PLGA 结合良好。包封率为 99%，药物释放呈渐进释放相，随后是较慢和持续释放相。虽然 HepG2 细胞对 PTX 的耐药性强于 MCF-7 细胞，但与 PTX 相比，两种细胞类型对 PTX-NPs 的反应性更强。IC50 值在乳腺癌细胞中从 19.3μg/ml 降至 6.7μg/ml，在肝癌细胞中从 42.5μg/ml 降至 13.1μg/ml。细胞凋亡是两种细胞的关键机制，至少有 44%的细胞发生凋亡。当细胞分别用 PTX-NPs 处理时，TXR1 的表达降低，同时 CYP3A4 和 CYP2C8 的表达增加。
综上所述，本体外研究报告了 MCF-7 和 HepG2 细胞对 PLGA 负载紫杉醇纳米粒的反应性增强与细胞对 PTX 的耐药性降低及其代谢增强之间的关联。
