title: Knockdown of snail sensitizes pancreatic cancer cells to chemotherapeutic agents and irradiation.
abstract: The prognosis of patients with pancreatic cancer remains poor; only patients with small tumors and complete resection have a chance of a complete cure. Pancreatic cancer responds poorly to conventional therapies, including chemotherapy and irradiation. Snail is a transcription factor that has been associated with anti-apoptotic and chemoresistant properties in pancreatic cancer cells. In this study, we investigated whether knockdown of Snail suppresses growth of and/or sensitizes pancreatic cancer cells to chemotherapeutic agents and irradiation through induction of apoptosis. An adeno-associated virus vector was used to deliver Snail siRNA and knockdown Snail expression in untreated pancreatic cancer cells and in pancreatic cancer cells treated with chemotherapeutic agents or γ-irradiation. Our data indicate that our adeno-associated virus vector can efficiently deliver Snail siRNA into PANC-1 cells both in vitro and in vivo, resulting in the knockdown of Snail expression at the mRNA and protein levels. We further show that knockdown of Snail expression results in potent growth suppression of pancreatic cancer cells and suppresses xenograft tumor growth in vivo through induction of apoptosis. Finally, knockdown of Snail expression significantly sensitizes pancreatic cancer cells to chemotherapeutic agents and γ-irradiation through induction of apoptosis. In conclusion, our findings indicate that Snail is an important modulator of therapeutic responses of pancreatic cancer cells and is potentially useful as a sensitizer in pancreatic cancer therapy.
authors: Department of General Surgery, The Affiliated Hospital of Medical College, QingDao University, Qing Dao, Shan Dong Province 266003, China; E-Mails: jiaoxuelong@163.com (X.J.); zhangzemi@126.com (X.L.); zlfzyj2009@163.com (Q.W.); wlsdermyy@163.com (D.Z.).
authors: Kejun
authors: K
authors: Zhang
authors: Xuelong
authors: X
authors: Jiao
authors: Xiaoyi
authors: X
authors: Liu
authors: Bingyuan
authors: B
authors: Zhang
authors: Jigang
authors: J
authors: Wang
authors: Quan
authors: Q
authors: Wang
authors: Yan
authors: Y
authors: Tao
authors: Dianliang
authors: D
authors: Zhang
references: J Histochem Cytochem. 2006 Nov;54(11):1263-75
references: 16899764
references: Nat Rev Cancer. 2007 Jun;7(6):415-28
references: 17508028
references: Oncologist. 2008 May;13(5):562-76
references: 18515741
references: Nat Rev Mol Cell Biol. 2002 Mar;3(3):155-66
references: 11994736
references: Hepatobiliary Pancreat Dis Int. 2008 Aug;7(4):345-56
references: 18693168
references: Gastroenterol Clin Biol. 2009 Oct-Nov;33(10-11):1028-35, e1-9
references: 19766418
references: Anticancer Drugs. 2008 Aug;19(7):655-71
references: 18594207
references: Curr Mol Med. 2008 Feb;8(1):12-37
references: 18289011
references: Cell. 2000 Jan 7;100(1):57-70
references: 10647931
references: Cancer Treat Rev. 2009 Aug;35(5):431-6
references: 19328630
references: Clin Cancer Res. 2007 Aug 15;13(16):4769-76
references: 17699854
references: Nihon Shokakibyo Gakkai Zasshi. 2009 Aug;106(8):1147-55
references: 19654461
references: Gan To Kagaku Ryoho. 2010 Mar;37(3):408-12
references: 20332676
references: Cell. 2002 Jan 25;108(2):153-64
references: 11832206
references: Apoptosis. 2000 Dec;5(6):491-507
references: 11303908
references: Genes Dev. 2004 May 15;18(10):1131-43
references: 15155580
references: Nat Med. 2004 Aug;10(8):789-99
references: 15286780
references: Cells Tissues Organs. 2007;185(1-3):191-203
references: 17587825
references: Curr Opin Oncol. 2004 Jan;16(1):19-24
references: 14685088
references: Cancer Res. 2005 Oct 15;65(20):9455-62
references: 16230409
references: Cancer Radiother. 2009 Sep;13(5):423-7
references: 19640763
references: Mol Cell Biol. 2004 Sep;24(17):7559-66
references: 15314165
references: Ann Surg Oncol. 2005 Jun;12(6):488-96
references: 15864483
references: Minerva Endocrinol. 2010 Mar;35(1):27-33
references: 20386525
references: Mol Cell Biol. 2001 Dec;21(23):8184-8
references: 11689706
references: Lung Cancer. 2008 Oct;62(1):8-14
references: 18372076
references: Development. 2005 Jul;132(14):3151-61
references: 15983400
references: Clin Cancer Res. 2003 Jul;9(7):2657-64
references: 12855644
references: Mol Cancer. 2008 Jul 24;7:64
references: 18652674
references: J Surg Res. 2007 Aug;141(2):196-203
references: 17583745