Gene interactions and pathways from curated databases and text-mining
Mol Cancer Ther 2006, PMID: 17121917

Statins induce mammalian target of rapamycin (mTOR)-mediated inhibition of Akt signaling and sensitize p53-deficient cells to cytostatic drugs.

Roudier, Emilie; Mistafa, Oras; Stenius, Ulla

Cholesterol-lowering statins have been shown to have anticancer effects in different models and sensitize human tumor cells to cytostatic drugs. We have investigated the effect of statins on Akt/protein kinase B signaling and the sensitizing effect of cytostatic drugs. It was found that insulin- and cytostatic drug-induced Akt phosphorylation and nuclear translocation was inhibited by pravastatin and atorvastatin in HepG2, A549, and H1299 cells in an mTOR-dependent manner. Statins also induced mTOR-dependent phosphorylation of insulin receptor substrate 1. In p53 wild-type cells (HepG2 and A549), pretreatment with statins did not sensitize cells to etoposide in concentrations which induced p53 stabilization. In line with our previous data, statins were found to attenuate the etoposide-induced p53 response. However, silencing p53 by RNA interference rescued the sensitizing effect. We also show that in a p53-deficient cell line (H1299), pretreatment with atorvastatin sensitized cells to etoposide, doxorubicin, and 5-fluorouracil and increased the level of apoptosis. Taken together, these data suggest that a mTOR-dependent, statin-induced inhibition of Akt phosphorylation and nuclear translocation sensitizes cells to cytostatic drugs. However, this effect can be counteracted in p53 competent cells by the ability of statins to destabilize p53.

Diseases/Pathways annotated by Medline MESH: Carcinoma, Hepatocellular, Liver Neoplasms
Document information provided by NCBI PubMed

Text Mining Data

Akt ⊣ mammalian target of rapamycin (mTOR): " Statins induce mammalian target of rapamycin (mTOR) mediated inhibition of Akt signaling and sensitize p53-deficient cells to cytostatic drugs "

Akt — mTOR: " It was found that insulin- and cytostatic drug induced Akt phosphorylation and nuclear translocation was inhibited by pravastatin and atorvastatin in HepG2, A549, and H1299 cells in an mTOR dependent manner "

insulin receptor substrate 1 → mTOR: " Statins also induced mTOR dependent phosphorylation of insulin receptor substrate 1 "

Akt ⊣ mTOR: " Taken together, these data suggest that a mTOR dependent , statin induced inhibition of Akt phosphorylation and nuclear translocation sensitizes cells to cytostatic drugs "

Akt — statin: " Taken together, these data suggest that a mTOR dependent , statin induced inhibition of Akt phosphorylation and nuclear translocation sensitizes cells to cytostatic drugs "

Manually curated Databases

No curated data.