Antisense oligonucleotides specific to mutated K-ras genes inhibit invasiveness of human pancreatic cancer cell lines.
OBJECTIVE
Point mutations of the K-ras gene are detected in > 90% of human pancreatic cancers and may play an important role in tumorigenesis. However, correlations between mutant K-ras and the invasive activity of the tumor have remained unclarified.


METHODS
17-merphosphorothioate antisense oligonucleotides targeting K-ras point mutations were transfected into three kinds of human pancreatic cancer cell lines (MIAPaCa-2, PANC-1, and BxPC-3), and the invasive activity was investigated using an in vitro chemoinvasion assay.


RESULTS
Antisense oligonucleotides strongly inhibited the invasive activity of the cell lines with mutant K-ras genes (MIAPaCa-2, PANC-1), but not in that with a wild-type K-ras (BxPC-3).


CONCLUSIONS
Antisense oligonucleotides specific to mutated K-ras genes inhibited the invasiveness of human pancreatic cancer cell lines. Specific antisense therapy to the point mutation of K-ras might be a new anticancer strategy for pancreatic cancer.
Third Department of Internal Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Y
Y
Nakada
S
S
Saito
K
K
Ohzawa
C Y
CY
Morioka
K
K
Kita
M
M
Minemura
T
T
Takahara
A
A
Watanabe
D015153:Blotting, Western; D002460:Cell Line; D004396:Coloring Agents; D004273:DNA, Neoplasm / Q000235:genetics; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000473:pathology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014162:Transfection; D014407:Tumor Cells, Cultured
D004396:Coloring Agents; D004273:DNA, Neoplasm; D016376:Oligonucleotides, Antisense; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue