Chemosensitivity induced by down-regulation of microRNA-21 in gemcitabine-resistant pancreatic cancer cells by indole-3-carbinol.
Anticancer Res. 2013 Apr ;33(4):1473-81. PMID: 23564788
Woo Hyun Paik
BACKGROUND/AIM: Overexpression of microRNA-21 (miR-21) indicates chemoresistance in pancreatic cancer. We evaluated the change of chemosensitivity to gemcitabine through the down-regulation of miR-21 in human pancreatic cancer cells (Panc-1).
MATERIALS AND METHODS: The efficacy of indole-3-carbinol (I3C) in suppressing miR-21 expression and its anticancer effect in combination with gemcitabine were investigated.
RESULTS: Down-regulation of miR-21 by I3C was positively-correlated in a time- and dose-dependent manner. I3C and gemcitabine combination therapy increased cytotoxicity in Panc-1 cells. Transfection of miR-21 mimic abrogated I3C-induced sensitivity to gemcitabine. DNA fragmentation and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays showed that pre-treatment with I3C enhanced apoptosis and this effect was attenuated by miR-21 transfection. The expression of programmed cell death-4 (PDCD4) was increased by I3C and reduced by miR-21 transfection.
CONCLUSION: I3C would be effective for enhancing sensitivity of pancreatic cancer cells to gemcitabine via down-regulation of miR-21. Such enhanced chemosensitivity might be explained by the increased expression of PDCD4, which is a downstream target which miR-21 negatively regulates.