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Antitumor effects of erythromycin and the related mechanism were investigated in the present study.Neuroblastoma cells (SH-SY5Y) were exposed to erythromycin at different concentrations for different durations.Cell proliferation was measured by cell counting,and cell viability was examined by MTT assay.Cell cycle phase distribution and the cytosolic calcium level were detected by flow cytometry.Mitochondrial membrane potential was measured by the JC-1 probe staining and fluorescent microscopy.The expression of an oncogene (c-Myc) and a tumor suppressor [p21 (WAF1/Cipl)] proteins was analyzed by using Western blotting.Erythromycin could inhibit the proliferation of SH-SY5Y cells in a concentration- and time-dependent manner.The cell cycle was arrested at S phase.Mitochon drial membrane potential collapsed and the cytosolic calcium was overloaded in SH-SY5Y cells when treated with erythromycin.The expression of c-Myc protein was down-regulated,while that of p21 (WAF1/Cip1) protein was up-regulated.It was concluded that erythromycin could restrain the proliferation of SH-SY5Y cells.The antitumor mechanism of erythromycin might involve regulating the expression ofc-Myc and p21 (WAF1/Cip1) proteins.