RT Journal Article
SR Electronic
T1 Chemosensitivity Induced by Down-regulation of MicroRNA-21 in Gemcitabine-resistant Pancreatic Cancer Cells by Indole-3-Carbinol
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 1473
OP 1481
VO 33
IS 4
A1 PAIK, WOO HYUN
A1 KIM, HYE REE
A1 PARK, JOO KYUNG
A1 SONG, BYEONG JUN
A1 LEE, SANG HYUB
A1 HWANG, JIN-HYEOK
YR 2013
UL http://ar.iiarjournals.org/content/33/4/1473.abstract
AB 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.