The anti-cancer effects of cisplatin on hepatic cancer are associated with modulation of miRNA-21 and miRNA-122 expression

摘要

OBJECTIVE: Cisplatin is an effective chemotherapeutic drug to treat hepatic cancer, but its efficacy is marred by extensive adverse effects. Micro (mi) RNAs are small regulatory RNAs that may be used as molecular targets to better fine-tune chemotherapy in hepatic cancer. In this study, we examined to what extent the anti-cancer effects of cisplatin are associated with expressions of miRNA (miR)-21 and miR-122. MATERIALS AND METHODS: The growth-inhibiting effects of cisplatin on the human hepatic cell line HepG2 were assessed by MTT assay, while cell apoptosis was documented using DAPI staining. Also, we tested the effects of cisplatin on tumour growth in a mouse tumour xenograft model. Finally, we quantified expression levels of miR-21 and miR-122 in cisplatin-treated HepG2 cells. RESULTS: We observed that cisplatin significantly decreased the growth of HepG2 cells (p < 0.05 vs control cells) at all tested concentration (5-80 μg/ml) after 24 or 48 hours of treatment. Microscopic studies demonstrated apoptotic signs in cisplatin-treated cells. In the mouse tumour xenograft model, tumour weights and volumes were significantly (p < 0.05 untreated animals) lower after treatment with cisplatin. Also, treatment of HepG2 cells for 48 hours with 20 μg/ml cisplatin was associated with significant decreases in miR-21 expression levels and up-regulation of miR-122. CONCLUSIONS: The anti-cancer effects of cisplatin are associated with down-regulation of miR-21 expression and up-regulation of miR-122.