博奕論壇轉載學醫札記
他汀類藥物通過抑制TGF-β影響人成膠質細胞瘤和其他癌症Statins affect human glioblastoma and other cancers through TGF-β inhibitionAizhen Xiao Breanna Brenneman Desiree Floyd Laurey Comeau Kelsey Spurio Inan Olmez Jeongwu LeeThe cholesterol-lowering statins have known anti-cancer effects錛 but the mechanisms and how to utilize statins in oncology have been unclear. We noted in the CellMiner database that statin activity against cancer lines correlated with higher expression of TGF-β target genes such as SERPINE1 and ZYX. This prompted us to assess whether statins affected TGF-β activity in glioblastoma (GBM)錛 a cancer strongly influenced by TGF-β and in dire need of new therapeutic approaches. We noted that statins reduced TGF-β activity錛 cell viability and invasiveness錛 Rho/ROCK activity錛 phosphorylation and activity of the TGF-β mediator Smad3錛 and expression of TGF-β targets ZYX and SERPINE1 in GBM and GBM-initiating cell (GIC) lines. Statins were most potent against GBM錛 GIC錛 and other cancer cells with high TGF-β activity錛 and exogenous TGF-β further sensitized mesenchymal GICs to statins. Statin toxicity was rescued by addition of exogenous mevalonolactone or geranylgeranyl pyrophosphate錛 indicating that the observed effects reflected inhibition of HMG CoA-reductase by the statins. Simvastatin significantly inhibited the growth of subcutaneous GIC grafts and prolonged survival in GIC intracranially grafted mice. These results indicate where the statins might best be applied as adjunct therapies in oncology錛 against GBM and other cancers with high TGF-β activity錛 and have implications for other statin roles outside of oncology.pmid: 30899443 Oncotarget 影響因子: 0.0 發表日期: 20190301 官網 免費下載很多老年人常規體檢,都被告之因頸動脈斑塊形成和高血壓,因此必須堅持服用阿伐他汀類藥物。此文有參考意義。轉載者附言,僅為自留,自閱,特此聲明。從前有座山,山上有座廟……這是許多故事的開端,也是我人生的開端。青石板,