RT Journal Article
SR Electronic
T1 Rho-Associated Protein Kinase (ROCK) Inhibitors Inhibit Survivin Expression and Sensitize Pancreatic Cancer Stem Cells to Gemcitabine
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 6311
OP 6318
VO 36
IS 12
A1 TAKEDA, HIROYUKI
A1 OKADA, MASASHI
A1 SUZUKI, SHUHEI
A1 KURAMOTO, KENTA
A1 SAKAKI, HIROTSUGU
A1 WATARAI, HIKARU
A1 SANOMACHI, TOMOMI
A1 SEINO, SHIZUKA
A1 YOSHIOKA, TAKASHI
A1 KITANAKA, CHIFUMI
YR 2016
UL http://ar.iiarjournals.org/content/36/12/6311.abstract
AB Background: Targeting pathways regulating survivin expression, which has been implicated in multidrug resistance of cancer cells, is a promising strategy to overcome cancer chemoresistance. To date, the role of rho-associated protein kinases (ROCKs) in survivin expression remains largely unknown. Materials and Methods: The effects of ROCK inhibitors Y-27632 and fasudil on survivin expression and cell viability were determined by immunoblot analysis and dye exclusion, respectively, in PANC-1 CSLC, a cancer stem cell line derived from a serum-cultured, gemcitabine-sensitive pancreatic cancer cell line, PANC-1. Results: siRNA-mediated knockdown of survivin revealed that the gemcitabine resistance of PANC-1 CSLC was dependent on survivin expression. Both Y-27632 and fasudil, reduced survivin expression in PANC-1 CSLC cells and sensitized them to gemcitabine. ROCK inhibition also reduced survivin expression in various other human cancer cell lines. Conclusion: Small molecule inhibitor-mediated targeting of ROCK may be a viable strategy to overcome cancer chemoresistance through down-regulation of survivin.