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The inhibition of SRC family kinase suppresses pancreatic cancer cell proliferation, migration, and invasion.
- Source :
-
Pancreas [Pancreas] 2014 Jul; Vol. 43 (5), pp. 768-76. - Publication Year :
- 2014
-
Abstract
- Objectives: Src is considered a rising therapeutic target for the treatment of solid tumors, and Src family kinases (SFKs) participate in cancer cell proliferation and survival. The role of SFK suppression was investigated in the proliferation, migration, and invasion of pancreatic cancer cells.<br />Methods: Knockdown of the SFKs in pancreatic cancer cells was achieved by transfecting small interfering RNAs, and its effects were investigated using proliferation, wound, and invasion assays.<br />Results: The SFK inhibitors suppressed proliferation and induced cell cycle arrest in pancreatic cancer cells. The SFK messenger RNA profiles showed that Yes1, Lyn, Fyn, Frk, Hck, and Src were expressed. Specific small interfering RNA transfection suppressed the messenger RNA expressions of Yes1, Lyn, Fyn, Frk, and Src, and the knockdown suppressed cell proliferation by 16.7% to 47.3% in PANC-1 cells. Knockdown of any of these 5 SFKs suppressed proliferation in other pancreatic cancer cell lines by 3.0% to 40.5%. The knockdowns significantly reduced pancreatic cancer cell migration by 24.9% to 66.7% and completely inhibited invasion.<br />Conclusions: These results suggest that the knockdown of Yes1, Lyn, Fyn, Frk, or Src reduce human pancreatic cancer cell proliferation, migration, and invasion, and that SFKs should be viewed as critical therapeutic targets of pancreatic cancer.
- Subjects :
- Blotting, Western
Cell Cycle genetics
Cell Line, Tumor
Humans
Neoplasm Invasiveness
Neoplasm Proteins antagonists & inhibitors
Neoplasm Proteins genetics
Neoplasm Proteins metabolism
Pancreatic Neoplasms genetics
Pancreatic Neoplasms metabolism
Pancreatic Neoplasms pathology
Protein-Tyrosine Kinases antagonists & inhibitors
Protein-Tyrosine Kinases genetics
Protein-Tyrosine Kinases metabolism
Proto-Oncogene Proteins c-fyn antagonists & inhibitors
Proto-Oncogene Proteins c-fyn genetics
Proto-Oncogene Proteins c-fyn metabolism
Proto-Oncogene Proteins c-hck antagonists & inhibitors
Proto-Oncogene Proteins c-hck genetics
Proto-Oncogene Proteins c-hck metabolism
Proto-Oncogene Proteins c-yes antagonists & inhibitors
Proto-Oncogene Proteins c-yes genetics
Proto-Oncogene Proteins c-yes metabolism
Proto-Oncogene Proteins pp60(c-src) antagonists & inhibitors
Pyrimidines pharmacology
Pyrroles pharmacology
Reverse Transcriptase Polymerase Chain Reaction
src-Family Kinases antagonists & inhibitors
src-Family Kinases metabolism
Cell Movement genetics
Cell Proliferation
RNA Interference
src-Family Kinases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1536-4828
- Volume :
- 43
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Pancreas
- Publication Type :
- Academic Journal
- Accession number :
- 24763074
- Full Text :
- https://doi.org/10.1097/MPA.0000000000000103