Suppression of invasion of a hamster pancreatic cancer cell line by antisense oligonucleotides mutation-matched to K-ras gene.
The anti-invasive activity of antisense oligonucleotides (ASO) specific to the K-ras gene in hamster pancreatic cancer was investigated. HaP-T1, a cell culture derived from BHP-induced hamster pancreatic cancer, was used. After liposome-mediated transfection with mutation-matched and mutation-mismatched ASO in different concentrations, cell proliferation was studied by MTT and MTT-agarose methods. In vitro chemoinvasion assay with the reconstitution of a matrix of a basement membrane onto a filter in a Boyden chamber was performed. Mutation-matched ASO inhibited the tumor growth and invasiveness of HaP-T1 in a dose-dependent manner, while mutation-mismatched ASO were not effective in inhibiting invasion. The present study suggests that antisense oligonucleotides mutation-matched to the K-ras gene may be a new anticancer strategy for pancreatic cancer since they inhibited not only tumor growth but also invasiveness in vitro.
Morioka
Cintia Yoko
CY
Department of Surgery, University of São Paulo, São Paulo, Brazil. morioka@gvmail.br
Machado
Marcel Cerqueira Cesar
MC
Saito
Seiji
S
Nakada
Yuji
Y
Matheus
André Siqueira
AS
Jukemura
José
J
Bacchella
Telesforo
T
Takahara
Terumi
T
Watanabe
Akiharu
A
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D006224:Cricetinae; D011905:Genes, ras; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*
D016376:Oligonucleotides, Antisense