I have also posted this on the Omega 3:6 thread “The traditional diet of Greece and cancer” but it is so significant I have reposted it as a separate item.
http://her2support.org/vbulletin/sho...d=1#post198943
I have long asked if Omega 6 has a role in HER2, and if herceptin somehow influences related pathways.
This trial proves Omega 6 product PGE2 has a role in HER2 by increasing HER expression. It is saying a reduction on PGE2 expression = a reduction in HER2 expression.
PGE 2 is made from Omega 6. IF you do not have an excess of Omega 6 in your system you will not make so much PGE2.
DHA is a more effective COX2 (PGE2) blocker than many drugs.
This is an excellent blog and Stephan is currently looking at Omega 6 and heart disease, and you might find the background helpful.
http://wholehealthsource.blogspot.com/
RB
Free Access
http://www.pubmedcentral.nih.gov/art...medid=19399184
AND within the paper
"As positive control for COX2 downregulation, cells were treated with the COX2-specific inhibitor Celecoxib® at 20 and 40 µM for 48 hours. 40 µM Celecoxib® significantly inhibited PGE2 production by more than 80% (p<0.001). Consistent with a prior report that PGE2 influences HER2 expression [29], we found that reduction of HER2 correlated to a reduction in PGE2 synthesis (Figure 3B)."
t10c12 conjugated linoleic acid suppresses HER2 protein and enhances apoptosis in SKBr3 breast cancer cells: possible role of COX2.
Flowers M, Thompson PA.
Department of Nutritional Sciences, University of Arizona, Tucson, AZ, USA.
mflowers@email.arizona.edu
BACKGROUND: HER2-targeted therapy with the monoclonal antibody trastuzumab (Herceptin) has improved disease-free survival for women diagnosed with HER2-positive breast cancers; however, treatment resistance and disease progression are not uncommon.
Current data suggest that resistance to treatment in HER2 cancers may be a consequence of NF-kappaB overexpression and
increased COX2-derived prostaglandin E2 (PGE(2)). Conjugated linoleic acid (CLA) has been shown to have anti-tumor properties and to inhibit NF-kappaB activity and COX2. METHODS: In this study, HER2-overexpressing SKBr3 breast cancer cells were treated with t10c12 CLA. Protein expression of the HER2 receptor, nuclear NF-kappaB p65, and total and phosphorylated IkappaB were examined by western blot and immunofluorescence. PGE(2) levels were determined by ELISA. Proliferation was measured by metabolism of 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), and apoptosis was measured by FITC-conjugated Annexin V staining and flow cytometry. RESULTS/CONCLUSIONS: We observed a significant decrease in HER2 protein expression on western blot following treatment with 40 and 80 microM t10c12 CLA (p<0.01 and 0.001, respectively) and loss of HER2 protein in cells using immunoflourescence that was most pronounced at 80 microM. Protein levels of nuclear NF-kappaB p65 were also significantly reduced at the 80 microM dose. This was accompanied by a significant decrease in PGE(2) levels (p = 0.05). Pretreatment with t10c12 CLA significantly enhanced TNFalpha-induced apoptosis and the anti-proliferative action of trastuzumab (p = 0.05 and 0.001, respectively). These data add to previous reports of an anti-tumor effect of t10c12 CLA
and suggest an effect on the HER2 oncogene that may be through CLA mediated downregulation of COX2-derived PGE(2).
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