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Keywords
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Adenocarcinoma, Fluoroquinolones, Systems biology, non-coding RNAs, RNA interference
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Abstract
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Ciprofloxacin antibiotics show anti-cancer effects against various cancer cells, partly by inhibiting topoisomerase II. However, ciprofloxacin can also potentiate the RNAi pathway and increase miRNA processing, which leads to the modulation of biological systems, including hub genes. Until now, the effects of ciprofloxacin at the RNAi-enhancing concentration (40 μg/mL) on non-small cell lung cancer (NSCLC) and its hub genes have not been investigated. This study aims to explore this effect. A549 cells, used as a model for NSCLC, were treated with 40 μg/mL ciprofloxacin, and the cytotoxicity, colony formation, migration, cell cycle, and apoptosis were evaluated. Hub genes of NSCLC and their miRNAs were identified using Gene Expression Omnibus database and bioinformatics analysis. The expression of two high-score hub genes and the miRNAs that target these hub genes was measured by qPCR. This study showed that ciprofloxacin resulted in a statistically significant reduction in cell viability of approximately 47% after 96 hours, a decrease in survival fraction by about 60%, and inhibition of cell migration by about 63% at 24 h. Additionally, ciprofloxacin induced G2/M phase cell cycle arrest and early apoptosis by approximately 10% and 30%, respectively, after 96 h. The expression of CCNB1 and CCNA2, the two high-scoring hub genes, significantly decreased, and the expression of miR-132-3p and miR-193-3p miRNAs, which could target CCNB1 and CCNA2, significantly increased (p< 0.05). These findings suggest that ciprofloxacin possesses anti-proliferative and anti-metastatic properties in NSCLC, potentially mediated through a dual mechanism involving Topoisomerase II inhibition and the modulation of the miRNA-CCNA2/CCNB1 axis.
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