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Title: Mevalonate pathway antagonist inhibits proliferation of serous tubal intraepithelial carcinoma and ovarian carcinoma in mouse models.      
keywords:
Transcriptome or Gene expression
ID:
PRJNA284267
description:
Statins are among the most frequently prescribed drugs because of their efficacy and low toxicity in treating hypercholesterolemia. Recently, statins have been reported to inhibit the proliferative activity of cancer cells, especially those with *TP53* mutations. Since *TP53* mutations occur in almost all of the ovarian high-grade serous carcinoma, we determined if statins suppressed tumor growth in animal models of ovarian cancer. Two ovarian cancer mouse models were employed. The first one was a genetically engineered model, mogp-TAg, in which the promoter of oviduct glycoprotein-1 was used to drive the expression of SV40 T-antigen in gynecologic tissues. These mice spontaneously develop serous tubal intraepithelial carcinomas (STICs), which are known as ovarian cancer precursor lesions. The second model was a xenograft tumor model in which human ovarian cancer cells were inoculated into immunocompromised mice. Mice in both models were treated with lovastatin, and effects on tumor growth were monitored. The molecular mechanisms underlying the anti-tumor effects of lovastatin were also investigated. Lovastatin significantly reduced the development of STICs in mogp-TAg mice and inhibited ovarian tumor growth in the mouse xenograft model. Knockdown of prenylation enzymes in the mevalonate pathway recapitulated the lovastatin-induced anti-proliferative phenotype. Transcriptome analysis indicated that lovastatin affected the expression of genes associated with DNA replication, Rho/PLC signaling, glycolysis, and cholesterol biosynthesis pathways, suggesting that statins have pleiotropic effects on tumor cells. The above results suggest that repurposing statin drugs for ovarian cancer may provide a promising strategy to prevent and manage this devastating disease. Overall design: SKOV3 and OVCAR5 cells were treated with either 10uM Lovastatin or DMSO for 48 hours before harvested for gene expression array.
accesstypes:
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA284267
authentication:
none
authorization:
none
ID:
pmid:26109099
name:
Homo sapiens
ncbiID:
ncbitax:9606
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject
  • R21 CA187512/CA/NCI NIH HHS/United States

  • P30 CA006973/CA/NCI NIH HHS/United States

  • R01 CA148826/CA/NCI NIH HHS/United States

  • CA165807/CA/NCI NIH HHS/United States

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