The Growth of A549 Cell Line is Inhibited by Pemetrexed Through Up-regulation of hsa-MiR-320a Expression.

Abstract

Background: Lung cancer deaths are increasing worldwide and the most common form of lung cancer treatment is chemotherapy. Pemetrexed (PMX) has been shown to be effective as a second-line treatment for advanced patients. Drugs can alter the expression of MicroRNAs, and MicroRNAs also can either enhance or reduce the drug's effectiveness and this is a two-way relationship. Hsa-MiR-320a is known to play a crucial role in the lung cancer. This study aims to investigate the expression of hsa-MiR-320a in lung cancer cells after treatment with PMX.

Materials and methods: A549 cells were cultured and treated with varying concentrations of PMX. Various parameters were measured, including cell viability, reactive oxygen species (ROS) production, lactate dehydrogenase (LDH) release, apoptosis assay, caspase 3 and 7 enzyme activity, and scratch assay. Additionally, gene expression profiles of hsa-MiR-320a, VDAC1, STAT3, BAX, and BCL2 were evaluated.

Results: PMX reduced the viability and increased apoptosis. After 48 h, ROS production was 3.366-fold higher than in control cells and the LDH release rate was increased by 39%. PMX also up-regulated the expression of hsa-MiR-320a by about 12-fold change.

Conclusion: Changes in the expression of MicroRNAs occur after chemotherapy, and these changes play a crucial role in regulating the growth of cancer cells. Identifying these MicroRNAs can be helpful in predicting the efficacy of the chemotherapy or introducing it as combination therapy. Our research has been shown that hsa-MiR-320a can serve as a biomarker of PMX efficacy and also has the potential to be used in combination therapy.