Article Text
Abstract
Background: Ras signalling is frequently aberrant in pancreatic cancer so that there is constitutive activation of the phosphatidylinositol 3-kinase (PI3K) and AKT/protein kinase B pathway, as well as the RAF/MEK/ERK pathway.
Aims: In the present study we investigated the role of the PI3K/AKT pathway in malignant transformation of pancreatic cancer cells.
Methods: A genetic approach was used to interfere with signal transduction in vitro and in vivo. RASN17, a dominant negative mutant of RAS, was applied to inhibit the PI3K/AKT pathway upstream of PI3K. The regulatory p85β subunit of PI3K and the negative regulator PTEN were utilised to inhibit the pathway at the level of PI3K, and AAA-AKT, a dominant negative mutant of AKT was employed to interfere with PI3K/AKT signalling at the level of AKT.
Results: Antiproliferative, proapoptotic, and anticancer effects were documented, showing that inhibition of the PI3K pathway in these cell lines suppresses tumour cell growth in vitro and reduces growth in nude mice.
Conclusions: The PI3K/AKT pathway represents a potential therapeutic target for pancreatic cancer, and gene therapy may be one approach to produce selective inhibition.
- PI3K, phosphatidylinositol 3-kinase
- DMEM, Dulbecco’s modified Eagle’s medium
- FCS, fetal calf serum
- PFU, plaque forming units
- MOI, multiplicity of infection
- MTS, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy-methoxyphenyl)-2-(4-sulfophenyl)-2H
- EGF, epidermal growth factor
- BSA, bovine serum albumin
- PBS, phosphate buffered saline
- pancreatic cancer
- ras oncogene
- gene therapy
Statistics from Altmetric.com
- PI3K, phosphatidylinositol 3-kinase
- DMEM, Dulbecco’s modified Eagle’s medium
- FCS, fetal calf serum
- PFU, plaque forming units
- MOI, multiplicity of infection
- MTS, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy-methoxyphenyl)-2-(4-sulfophenyl)-2H
- EGF, epidermal growth factor
- BSA, bovine serum albumin
- PBS, phosphate buffered saline
Footnotes
-
Conflict of interest: None declared.