Eugenol-loaded mesoporous silica nanoparticles enhance the sensitivity of cisplatin against AGS human gastric adenocarcinoma cell line

Gastric cancer is one of the most common cancers with a high mortality rate worldwide. Eugenol possesses antioxidant, anti-inflammatory, antimicrobial, and anticancer properties. Mesoporous silica nanoparticles (MSN) have been promising carriers for drug delivery. This study aimed to investigate the synergism effect of free eugenol/eugenol-MSN and cisplatin on the AGS human gastric adenocarcinoma cell line. In this study, MSN was synthesized and loaded with eugenol. Cultured AGS cells were treated with different concentrations of free eugenol/eugenol-MSN individually and in combination with cisplatin. MTT assay, scratch assay, and flow cytometry were employed to assess cell viability, migration, and apoptosis. The antioxidant properties of free eugenol/eugenol-MSN and their effect on superoxide dismutase (SOD) activity were evaluated. Real-time PCR was used to study the effect of free eugenol/eugenol-MSN on the expression of metastatic pathway genes such as MMP2, MMP9, and KRAS, and some genes involved in apoptosis including caspase 3, caspase 8, and caspase 9. A synergism effect of free eugenol/eugenol-MSN and cisplatin (CI < 1) was observed. Combination therapies were significantly more effective in cell growth reduction, migration inhibition, and apoptosis induction than single treatments. Free eugenol has more potential in DPPH radical scavenging, and eugenol-MSN has more potential in increasing SOD activity. The relative expression of caspase 3, caspase 8, and caspase 9 genes in the treated cells increased compared to the control group, and the expression of MMP2, MMP9, and KRAS oncogenes decreased significantly. Eugenol loading in MSN leads to increasing the sensitivity of cisplatin against gastric cancer.