title: Simvastatin and Atorvastatin inhibit DNA replication licensing factor MCM7 and effectively suppress RB-deficient tumors growth.
abstract: Loss or dysfunction of tumor suppressor retinoblastoma (RB) is a common feature in various tumors, and contributes to cancer cell stemness and drug resistance to cancer therapy. However, the strategy to suppress or eliminate Rb-deficient tumor cells remains unclear. In the present study, we accidentally found that reduction of DNA replication licensing factor MCM7 induced more apoptosis in RB-deficient tumor cells than in control tumor cells. Moreover, after a drug screening and further studies, we demonstrated that statin drug Simvastatin and Atorvastatin were able to inhibit MCM7 and RB expressions. Further study showed that Simvastatin and Atorvastatin induced more chromosome breaks and gaps of Rb-deficient tumor cells than control tumor cells. In vivo results showed that Simvastatin and Atorvastatin significantly suppressed Rb-deficient tumor growth than control in xenograft mouse models. The present work demonstrates that 'old' lipid-lowering drugs statins are novel weapons against RB-deficient tumors due to their effects on suppressing MCM7 protein levels.
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, Shaanxi, China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, Shaanxi, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, Shaanxi, China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, Shaanxi, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, Shaanxi, China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, Shaanxi, China.
authors.forename: Zheyong
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, Shaanxi, China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, Shaanxi, China.
authors.forename: Fang
authors.initials: F
authors.lastname: He
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, Shaanxi, China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, Shaanxi, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, Shaanxi, China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, Shaanxi, China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, Shaanxi, China.
authors.forename: Yina
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, Shaanxi, China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, Shaanxi, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, Shaanxi, China.
authors.forename: Can
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, Shaanxi, China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, Shaanxi, China.
authors.forename: Yaochun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, Shaanxi, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo 14263, NY 14263, USA.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston 02118, MA, USA.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Vaziri
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, Shaanxi, China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, Shaanxi, China.
authors.forename: Peijun
authors.initials: P
authors.lastname: Liu
mesh_terms: D000818:Animals; D000069059:Atorvastatin / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects*; D006801:Humans; D051379:Mice; D064168:Minichromosome Maintenance Complex Component 7 / Q000378:metabolism*; D012175:Retinoblastoma / Q000188:drug therapy* / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D018797:Cell Cycle Proteins; D016160:Retinoblastoma Protein; D000069059:Atorvastatin; D019821:Simvastatin; D064168:Minichromosome Maintenance Complex Component 7