Article thumbnail

Knockdown of Snail Sensitizes Pancreatic Cancer Cells to Chemotherapeutic Agents and Irradiation

By Kejun Zhang, Xuelong Jiao, Xiaoyi Liu, Bingyuan Zhang, Jigang Wang, Quan Wang, Yan Tao and Dianliang Zhang


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

Topics: Article
Publisher: Molecular Diversity Preservation International (MDPI)
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. (2010). Aberrant expression of the transcription factors Snail and slug alters the response to genotoxic stress.
  2. (2004). Apoptosis in human cancer cells.
  3. (2002). Apoptosis: A link between cancer genetics and chemotherapy. Cell
  4. (2008). Apoptotic pathways in pancreatic ductal adenocarcinoma. Mol Cancer.
  5. (2004). Cancer genes and the pathways they control.
  6. (2005). Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition. Cancer Res.
  7. (2007). Epithelial to mesenchymal transition: Expression of the regulators snail, slug, and twist in pancreatic cancer. Clin. Cancer Res.
  8. (2007). Expression of snail in pancreatic cancer promotes metastasis and
  9. (2005). Expression of the transcription factors snail, slug, and twist and their clinical significancein human breast cancer.
  10. (2009). Genetic alterations in precancerous pancreatic lesions and their clinical implications.
  11. (2009). Intraoperative radiotherapy: Back to the future? Cancer Radiother.
  12. (2010). Kagaku Ryoho
  13. (2008). Knockdown of Snail, a novel zinc finger transcription factor, via RNA interference increases A549 cell sensitivity to cisplatin via JNK/mitochondrial pathway. Lung Cancer
  14. (2008). Metastatic pancreatic cancer 2008: Is the glass less empty. Oncologist
  15. Molecular aspects of carcinogenesis in pancreatic cancer. Hepatobiliary Pancreat Dis.
  16. (2010). Molecular therapy of pancreatic cancer. Minerva Endocrinol.
  17. (2008). Neurotransmission and cancer: Implications for prevention and therapy. Anticancer Drugs
  18. (2008). New aspects of regulatory signaling pathways and novel therapies in pancreatic
  19. (2009). Pancreatic cancer: Current and future treatment strategies. Cancer Treat. Rev.
  20. (2009). Pancreatitis-associated genes and development of pancreatic cancer. Nippon Shokakibyo Gakkai Zasshi
  21. (2004). Snail blocks the cell cycle and confers resistance to cell death. Genes Dev.
  22. (2006). Snail-dependent and -independent epithelial-mesenchymal transition in oral squamous carcinomacells.
  23. (2000). The hallmarks of cancer. Cell
  24. (2000). The molecular control of DNA damage-induced cell death. Apoptosis
  25. (2001). The mouse snail gene encodes a key regulator of the epithelial-mesenchymal transition. Mol. Cell Biol.
  26. (2005). The Snail genes as inducers of cell movement and survival: Implications in development and cancer. Development
  27. The snail superfamily of zinc-finger transcription factors.
  28. (2003). Transcriptional repressor snail and progression of human hepatocellular carcinoma. Clin. Cancer Res.
  29. (2007). Vimentin and epithelial-mesenchymal transition in human breast cancer observations in vitro and in vivo. Cells Tissues Organs
  30. (2007). Zeb and bHLH factors in tumour progression: An alliance against the epithelial phenotype?