Inhibitory Effect of Macrolide Antibiotics on Invasion and Proliferation of Lung Cancer Cell Lines

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It has recently been speculated that macrolide antibiotics have an antineoplastic effect besides their antimicrobial one, but the exact mechanism is unknown. We examined the effect of macrolides on invasion of carcinoma cells. Cell lines PA-1, HT-1080, A-549 and SBC-3 were used. For macrolide antibiotics, clarithromycin (CAM) and Azythromycin (AZM) were used at 10 μg/ml. The effect of macrolides on cell invasion was estimated by using a MATRIGEL invasion chamber. Both CAM and AZM inhibited the invasion of all cell lines. Moreover, both macrolides inhibited the invasion of adenocarcinoma cells which were separated from the pleural effusion of patients with lung carcinoma. To determine the mechanism of inhibitory effect on invasion, the effect of macrolides on eell adhesion was estimated by using a MATRIGEL coated plate and crystal violet staining technique. Both CAM and AZM inhibited the cell adhesion in all cell lines. The expression of CD49c, one of the adhesion molecules belonging to the integrin family, was also investigated in A-549 and SBC-3 by flow cytometry. CAM significantly reduced the CD49c expression, but AZM did not. Anti-CD49c monoclonal antibody inhibited the invasion of A-549 and SBC-3. Inversely, AZM but not CAM inhibited the proliferation of HT-1080 and PA-1 by using of MTT assay, and increased the apoptosis of both cell lines by using of ELISA.These results suggest that macrolides suppress the invasion of carcinoma cells partly through inhibition of cell adhesion and through increase of cell apoptosis.