title: Simvastatin downregulates expression of TGF-βRII and inhibits proliferation of A549 cells via ERK.
abstract: Lung cancer is the leading cause of cancer-related death worldwide. Transforming growth factor-β receptor II (TGF-βRII) plays an important role in the regulation of proliferation and progression in cancer. Statins have been documented to exhibit anticancer and cancer chemopreventive properties. However, the effects and mechanisms of simvastatin on the development of lung cancer are still unclear. In the present study, quiescent A549 cells were treated in vitro with fetal bovine serum (FBS) in the presence or absence of simvastatin. MTT, Western blot, and real-time qPCR were used to detect cell viability, activation of ERK, and expression of TGF-βRII at the protein and RNA level. Our results demonstrated that simvastatin inhibited activation of ERK, downregulated expression of TGF-βRII, and suppressed A549 cell proliferation. Furthermore, the effects of simvastatin can be reversed by farnesyl pyrophosphate (FPP). Therefore, these results suggest that simvastatin may inhibit A549 cell proliferation and downregulate TGF-βRII expression by inhibiting activation of ERK. Our findings may advance the current understanding of the effects of simvastatin on cancer progression and contribute to the study of cancer treatment.
authors: Nursing Division, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, 264100, China.
authors: Li
authors: L
authors: Shang
authors: Shu-Shan
authors: SS
authors: Jia
authors: Hai-Ming
authors: HM
authors: Jiang
authors: Hua
authors: H
authors: Wang
authors: Wen-Hua
authors: WH
authors: Xu
authors: Chang-Jun
authors: CJ
authors: Lv
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011106:Polyisoprenyl Phosphates / Q000008:administration & dosage; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D012717:Sesquiterpenes / Q000008:administration & dosage; D019821:Simvastatin / Q000008:administration & dosage*
chemical_list: D011106:Polyisoprenyl Phosphates; D018125:Receptors, Transforming Growth Factor beta; D012717:Sesquiterpenes; C004808:farnesyl pyrophosphate; D019821:Simvastatin; D017346:Protein Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II
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