Boosting Antitumor Activity: CuO Nanoparticles Enhance Pemetrexed Efficacy and Increase hsa-miR-548c-3p Expression in Human Lung Cancer

Background and objective — Lung cancer, particularly non-small cell lung cancer (NSCLC), is a leading cause of cancer-related death. Pemetrexed (PEM) is recognized as an effective chemotherapy drug. However, its efficacy is often compromised by resistance and side effects. Copper oxide nanoparticles (CuO NPs) are promising agents due to their unique characteristics, which can improve drug delivery and cytotoxicity. The objective of this study was to evaluate the simultaneous effect of CuO NPs on enhancing the antitumor activity of PEM in human lung cancer cells and to investigate changes in hsa-miR-548c-3p expression in lung cancer cells. Methods — After culturing A549 cancer cells, various concentrations of PEM and CuO NPs were applied to determine the IC50 value. The cells were then exposed to half the IC50 concentration of PEM, both with and without CuO NPs, for 48 h. The assessment included measurements of cell viability, apoptosis, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS), and the relative expression levels of hsa-miR-548c-3p, TYMS, CASP8, and CASP9. Results — The study showed that concomitant use of PEM with CuO NPs nanoparticles resulted in decreased cell viability (P<0.05) and increased apoptosis, ROS production, and LDH release compared with the control group and the group receiving the either drug alone (P<0.05). Concomitant use also increased the expression of hsa-miR-548c-3p, CASP8, and CASP9 (P<0.05), while decreasing TYMS expression compared with the control group (P<0.05). Conclusion — Based on the results of this study, it can be concluded that the combination of CuO NPs with PEM may enhance the efficacy of the latter chemotherapeutic drug.