https://www.mdu.se/

Abstract

Activation of the PI3K/Akt signaling cascade is often associated with advanced forms of prostate cancer cells, DU145. This is likely explained by the common loss of the PTEN gene in majority of cancer cells. This study have documented that low concentration of atorvastatin, a drug inhibiting HMG-CoA reductase and cholesterol metabolism, decreased the level of insulin-induced phosphorylated Akt in the nucleus.

The statins effect on Akt/protein kinase B signaling and the sensitizing effect of cytostatic drugs have been investigated in this study and it were found that cytostatic drugs induced Akt phosphorylation and nuclear translocation was inhibited by atorvastatin in A549 and DU145 cells. Inhibition of PI3K with LY294002 was observed by MTT assay, and it were noticed that atorvastatin increased the effect of LY294002.

The main point of the study was the localization of the tumor suppressor PTEN. This gene acts as a plasma-membrane lipid-phosphatase antagonizing the phosphoinositide 3-kinase/Akt cell survival pathway. The nuclear localization of PTEN is a central for its activity. The insulin-induced A549 cells were treated with atorvastatin, thereafter very rapid change in PTEN localization was observed.

The study is preformed in view of good laboratory practice, GLP. In this study GLP applies to non-clinical experiment conducted for the assessment of the safety of chemicals (the concentration of the atorvastatin) to man and the environment.