The incidence and mortality rates from esophageal adenocarcinoma are rapidly increasing in the western world.
Chemoprevention is being advocated to reduce the burden of disease.
|Simvastatin inhibited activation of extracellular signal-regulated kinase|
|American Journal of Gastroenterology|
Statins are used clinically to treat hypercholesterolemia, and have an excellent safety profile.
Statins reduce the intracellular availability of several biosynthetic intermediates important in intracellular signaling.
Dr Olorunseun Ogunwobi and colleagues from the United Kingdom hypothesized that statins may effect esophageal adenocarcinoma proliferation or apoptosis.
The team studied the OE33 and BIC-1 esophageal adenocarcinoma cell lines and simvastatin, lovastatin, and pravastatin.
Proliferation was quantified by thiazoyl blue colormetric and bromodeoxyuridine incorporation assays.
Apoptosis was determined using assays for intracellular nucleosomes and caspase-3 activity.
Detection of phosphorylated kinases, affinity precipitation, immunoblotting, and reverse transcriptase-polymerase chain reaction were used to determine the effects on intracellular signaling.
The researchers found that all 3 statins reduced viable cell number, and inhibited proliferation in a similar dose-dependent manner.
Statins induced apoptosis and enhanced the antiproliferative effect of NS-398, a selective cyclooxygenase-2 inhibitor.
The effects were dependent on farnesylation, but not geranylgeranylation, of intracellular targets, and statins reduced serum-stimulated Ras activity.
Simvastatin inhibited activation of extracellular signal-regulated kinase, and protein kinase B.
However, treatment increased messenger RNA, and protein expression of the proapoptotic proteins Bax and Bad.
The research team observed that protein levels of the antiapoptotic proteins B-cell lymphoma (Bcl)-2 and Bcl-XL were unchanged.
Dr Ogunwobi's team concluded, "Statins inhibit proliferation and induce apoptosis in esophageal adenocarcinoma cells via inhibition of Ras farnesylation, and inhibition of the extracellular signal-regulated kinase and Akt signaling pathways."
"Statins may have some potential as chemopreventative and adjuvant chemotherapeutic agents in esophageal adenocarcinoma."