AlMotwaa Sahar M, Al-Otaibi Waad A
Department of Chemistry, College of Science and Humanities, Shaqra University, P.O. Box 6974, Al Quwayiyah 19257, Saudi Arabia.
Pharmaceutics. 2022 Jun 24;14(7):1336. doi: 10.3390/pharmaceutics14071336.
The limitations of gemcitabine (GEM) in cancer therapy are due to its poor pharmacokinetics, which cause undesired adverse effects. The current study was aimed at investigating the anticancer effect and apoptotic mechanism of synthesized nanoemulsion (NE) containing essential oil (PC-EO) and GEM (PC-NE:GEM) on MCF-7 and Hep-G2 cancer cell lines. An optimized NE formulation was selected based on the Box-Behnken method. The droplet size of the optimized PC-NE was 9.93 ± 0.53 nm, but after GEM loading, it was increased to 11.36 ± 0.0.21 nm. Results from FTIR revealed that GEM was successfully loaded onto PC-NE. The antineoplastic effect of PC-NE:GEM on MCF-7 and Hep-G2 cancer cells was increased more than 100-fold relative to that of GEM. A combination index and isobologram based on CompuSyn software revealed the synergistic effect of the formulation produced by a 1:1 ratio combination of PC-NE and GEM. These findings were confirmed by examination of cellular morphologies. The combination formulation strongly induced about 4.48-fold and 2.95-fold increases in apoptosis in MCF-7 and Hep-G2 cells, respectively, when compared with GEM. Moreover, PC-NE:GEM produced a synergistic increase in ROS production in MCF-7 cells (15.23%) and Hep-G2 cells (31.69%), when compared with GEM. In addition, PC-NE:GEM enhanced the activation of the intrinsic apoptosis pathway through upregulation of expressions of p53 and Caspase-3, and downregulation of Bcl-2 expression in MCF-7 cells, while the expressions of Caspase-3, Bax, and p53 were upregulated in HepG2 cells. These results indicate that the GEM-loaded NE containing PC-EO may reduce the dose of GEM and eliminate the associated side effects.
吉西他滨（GEM）在癌症治疗中的局限性归因于其较差的药代动力学，这会导致不良副作用。本研究旨在探究含有精油（PC-EO）和GEM的合成纳米乳剂（NE）（PC-NE:GEM）对MCF-7和Hep-G2癌细胞系的抗癌作用及凋亡机制。基于Box-Behnken方法选择了优化的NE配方。优化后的PC-NE液滴尺寸为9.93±0.53nm，但负载GEM后增加到11.36±0.021nm。傅里叶变换红外光谱（FTIR）结果表明GEM成功负载到PC-NE上。与GEM相比，PC-NE:GEM对MCF-7和Hep-G2癌细胞的抗肿瘤作用增强了100多倍。基于CompuSyn软件的联合指数和等效线图显示PC-NE与GEM按1:1比例组合产生的制剂具有协同作用。这些发现通过细胞形态学检查得到证实。与GEM相比，联合制剂分别强烈诱导MCF-7和Hep-G2细胞凋亡增加约4.48倍和2.95倍。此外，与GEM相比，PC-NE:GEM使MCF-7细胞（15.23%）和Hep-G2细胞（31.69%）中的活性氧（ROS）产生协同增加。此外，PC-NE:GEM通过上调p53和Caspase-3的表达以及下调MCF-7细胞中Bcl-2的表达来增强内源性凋亡途径的激活，而HepG2细胞中Caspase-3、Bax和p53的表达上调。这些结果表明含有PC-EO的负载GEM的NE可能降低GEM的剂量并消除相关副作用。
