PT  - JOURNAL ARTICLE
AU  - TAKEDA, HIROYUKI
AU  - OKADA, MASASHI
AU  - SUZUKI, SHUHEI
AU  - KURAMOTO, KENTA
AU  - SAKAKI, HIROTSUGU
AU  - WATARAI, HIKARU
AU  - SANOMACHI, TOMOMI
AU  - SEINO, SHIZUKA
AU  - YOSHIOKA, TAKASHI
AU  - KITANAKA, CHIFUMI
TI  - Rho-Associated Protein Kinase (ROCK) Inhibitors Inhibit Survivin Expression and Sensitize Pancreatic Cancer Stem Cells to Gemcitabine
DP  - 2016 Dec 01
TA  - Anticancer Research
PG  - 6311--6318
VI  - 36
IP  - 12
4099  - http://ar.iiarjournals.org/content/36/12/6311.short
4100  - http://ar.iiarjournals.org/content/36/12/6311.full
SO  - Anticancer Res2016 Dec 01; 36
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.