Lentivirus-mediated shRNA targeting XIAP and survivin inhibit SW1990 pancreatic cancer cell proliferation in vitro and in vivo.

Abstract

The aim of this study was to investigate the inhibitor of apoptosis proteins survivin and XIAP in pancreatic cancer by determining their biological characteristics and expression. XIAP and survivin are potential therapeutic targets for pancreatic cancer, and elucidating their association with cell proliferation and apoptosis may lead to the development of novel treatments for this disease. The human pancreatic cancer SW1990 cell line was infected with lentivirus and then analyzed by real-time PCR, and the results were confirmed by Western blotting. The MTT assay and the determination of caspase-3/-7 activity, DAPI-staining and tumorigenicity were used to measure cell proliferation and apoptosis in the human pancreatic cancer SW1990 cell line and in an experimental pancreatic cancer mouse xenograft model inoculated with the lentivirus-transfected SW1990 cells. The results revealed that the XIAP and survivin proteins were differentially expressed among the pancreatic cancer cell lines, and their decreased expression resulted in the inhibition of cell proliferation in vitro as well as in vivo. These findings suggest that lentivirus-mediated gene therapy targeting XIAP and survivin is a potential and attractive strategy for the treatment of pancreatic cancer.

• Authors: Chun Jiang, Tan Tan, Xiao-Ping Yi, Hong Shen, Yi-Xiong Li
• Journal: Molecular medicine reports (Mol Med Rep) 2011 Jul-Aug Vol. 4 Issue 4 Pg. 667-74 ISSN: 1791-3004 [Electronic] Greece
• PMID: 21479361 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BIRC5 protein, human
• Inhibitor of Apoptosis Proteins
• RNA, Small Interfering
• Survivin
• X-Linked Inhibitor of Apoptosis Protein
• Caspase 3
• Caspase 7

Topics

• Animals
• Apoptosis
• Caspase 3 (metabolism)
• Caspase 7 (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Genetic Therapy
• Genetic Vectors (chemistry, metabolism)
• Humans
• Inhibitor of Apoptosis Proteins (antagonists & inhibitors, genetics, metabolism)
• Lentivirus (genetics)
• Mice
• Pancreatic Neoplasms (metabolism, therapy)
• RNA Interference
• RNA, Small Interfering (metabolism)
• Survivin
• Transplantation, Heterologous
• X-Linked Inhibitor of Apoptosis Protein (antagonists & inhibitors, genetics, metabolism)