Dataset Information

Simvastatin and metformin inhibit cell growth in hepatitis C virus infected cells via mTOR increasing PTEN and autophagy.

ABSTRACT: Hepatitis C virus (HCV) infection has been related to increased risk of development of hepatocellular carcinoma (HCC) while metformin (M) and statins treatment seemed to protect against HCC development. In this work, we aim to identify the mechanisms by which metformin and simvastatin (S) could protect from liver cancer. Huh7.5 cells were infected with HCV particles and treated with M+S. Human primary hepatocytes were treated with M+S. Treatment with both drugs inhibited Huh7.5 cell growth and HCV infection. In non-infected cells S increased translational controlled tumor protein (TCTP) and phosphatase and tensin homolog (PTEN) proteins while M inhibited mammalian target of rapamycin (mTOR) and TCTP. Simvastatin and metformin co-administered down-regulated mTOR and TCTP, while PTEN was increased. In cells infected by HCV, mTOR, TCTP, p62 and light chain 3B II (LC3BII) were increased and PTEN was decreased. S+M treatment increased PTEN, p62 and LC3BII in Huh7.5 cells. In human primary hepatocytes, metformin treatment inhibited mTOR and PTEN, but up-regulated p62, LC3BII and Caspase 3. In conclusion, simvastatin and metformin inhibited cell growth and HCV infection in vitro. In human hepatocytes, metformin increased cell-death markers. These findings suggest that M+S treatment could be useful in therapeutic prevention of HCV-related hepatocellular carcinoma.

SUBMITTER: Del Campo JA

PROVIDER: S-EPMC5791999 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundNonsmall-cell lung cancer (NSCLC) is the main type of lung cancer, whose morbidity and mortality rank first among malignant tumors. More than 70% of NSCLC patients are diagnosed at locally advanced or advanced stage, missing the best operation period. Chemotherapy and targeted therapy are important means for the treatment of advanced NSCLC, but various side effects seriously affect the curative effect and the life quality of NSCLC patients. Our previous clinical practice has shown that Mufangji Decoction, a classic traditional Chinese medicine, has a significant curative effect in the treatment of NSCLC, but the specific mechanism is not clear. This study intends to explore the potential mechanism of Mufangji Decoction and its active ingredient patchouli alcohol against NSCLC and to provide a scientific basis for the prevention and treatment of NSCLC by traditional Chinese medicine.MethodsThe in vivo and in vitro experiments were performed to evaluate the antitumor effects and investigate the underlying mechanism of Mufangji Decoction and its active ingredient patchouli alcohol. Network pharmacology was applied to analyze the effective ingredients and potential targets or signaling pathways of Mufangji Decoction.ResultsOur current study shows that Mufangji Decoction can effectively inhibit the growth of subcutaneous transplantation of NSCLC. The following network pharmacological analysis and in vivo experiment suggest that patchouli alcohol is one of the main active ingredients of Mufangji Decoction and exerts antitumor effects. Further mechanism investigation reveals that the antitumor effect of patchouli alcohol is related to the induction of Akt/mTOR signaling pathway-mediated autophagy in NSCLC cells.ConclusionMufangji Decoction and its active ingredient patchouli alcohol might exert their antitumor effects in NSCLC partly through regulating Akt/mTOR-mediated autophagy, providing the evidence that traditional Chinese medicine might be a key approach for NSCLC treatment via targeting the Akt/mTOR signal axis.

Dataset Information

Simvastatin and metformin inhibit cell growth in hepatitis C virus infected cells via mTOR increasing PTEN and autophagy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets