Introduction and Objective: Ciprofloxacin as a broad-spectrum antibiotic has shown anti-cancer effects against various cells, including non-small cell lung cancer (NSCLC). This effect has been related to inhibition of the enzyme topoisomerase II. However, ciprofloxacin has been reported that able to potentiate the RNAi pathway and increase miRNA processing at lower concentrations (150 μM) of topoisomerase inhibitors. However, the effects of ciprofloxacin at this concentration on NSCLC have not been investigated. Therefore, in this study, we investigated the effect of ciprofloxacin on A549 cells as a model of NSCLC and the expression of some genes and miRNAs involved in this cancer.
Materials and Methods: We evaluate the effect of ciprofloxacin on survival rate, cell migration and colony formation in A549 cell line. We studied cell cycle and apoptosis in 150 μM concentration in 96 h by Flow cytometry. Hub genes and their miRNAs were identified by bioinformatics analysis. Expression of hub genes and miRNAs in treatment and control cells were measured by real-time PCR.
Results: The results of this study showed that ciprofloxacin at a concentration of 150 μM leads to a decrease in survival rate (47% in 96 hours, p <0.001), cell migration and colony formation in A549 cell line. It was also observed that ciprofloxacin increases the cell population in the G2/M phase about 10% at a concentration of 150 μM during 96 hours; But it induces apoptosis in about 55% of cells. The expression of miR-132-3p and miR-193-3p miRNAs increased under the influence of this drug and the expression of CCNB1 and CCNA2 hub genes decreased (P <0.05).
Discussion and Conclusion: Ciprofloxacin at a concentration of 150 μM has little effect on the population of S-phase cells. Probably, another mechanism except inhibition of topoisomerase II involved in the induction of apoptosis, which is possible that increased expression of miR-132-3p and miR-193-3p amplifying the RNAi pathway at this concentratio
