关键词: miR-1208, 胰腺癌, 吉西他滨化疗

Abstract: Objective To investigate the impact of gemcitabine onmiR-1208 expression and to elucidate the molecular mechanism of gemcitabine holding its inhibitory effect on glycolysis in human pancreatic cancer (PC) cell lines. Methods Real-time PCR analysis was employed to determine the expression levels of miR-1208 in PC tissues and PC cell lines. The cell growth, the cellular lactate production, and the glucose consumption were detected using CCK-8 assay, Lactate detection Kit, and Glucose detection Kit in BxPC-3 and PANC-1 PC cell lines. The correlation between gemcitabine treatment, miR-1208, and the metabolic shift of PC cells through a rescue assay. Results MiR-1208 expression depicts a significant downregulation in PC tissues (60%, 12/20) (P<0.05).Enforced expression of miR-1208 inhibits the cell growth, the cellular lactate production, and the glucose consumption in BxPC-3 and PANC-1 cell lines. The expression of LDH-A and LDH-D is downregulated in these two cell lines with miR-1208 overexpression (P<0.01). The expression of miR-1208 is upregulated in gemcitabine-treated PC cell lines, whereas the expression of LDH-A/D is downregulated in PC cell lines with the same treatment. Rescue assay indicates that miR-1208 inhibition to prevent its induction by gemcitabine treatment leads to increased cellular lactate production and glucose consumption in PC cells. Conclusions Gemcitabine represents its suppressive effect on glycolysis at least partly via triggering the expression of miR-1208 in PC cells.

Key words: miR-1208, pancreatic cancer, gemcitabine chemotherapy