他汀类药物通过抑制TGF-β影响人成胶质细胞瘤和其他癌症

Statins affect human glioblastoma and other cancers through TGF-β inhibition

Aizhen Xiao   Breanna Brenneman   Desiree Floyd   Laurey Comeau   Kelsey Spurio   Inan Olmez   Jeongwu Lee  

The cholesterol-lowering statins have known anti-cancer effects, 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), a cancer strongly influenced by TGF-β and in dire need of new therapeutic approaches. We noted that statins reduced TGF-β activity, cell viability and invasiveness, Rho/ROCK activity, phosphorylation and activity of the TGF-β mediator Smad3, and expression of TGF-β targets ZYX and SERPINE1 in GBM and GBM-initiating cell (GIC) lines. Statins were most potent against GBM, GIC, and other cancer cells with high TGF-β activity, and exogenous TGF-β further sensitized mesenchymal GICs to statins. Statin toxicity was rescued by addition of exogenous mevalonolactone or geranylgeranyl pyrophosphate, 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, against GBM and other cancers with high TGF-β activity, and have implications for other statin roles outside of oncology.

pmid: 30899443 Oncotarget 影响因子: 0.0 发表日期: 20190301 官网 免费下载

很多老年人常规体检，都被告之因颈动脉斑块形成和高血压，因此必须坚持服用阿伐他汀类药物。此文有参考意义。转载者附言，仅为自留，自阅，特此声明。