title: Nifedipine promotes the proliferation and migration of breast cancer cells.
abstract: Nifedipine is widely used as a calcium channel blocker (CCB) to treat angina and hypertension,but it is controversial with respect the risk of stimulation of cancers. In this study, we demonstrated that nifedipine promoted the proliferation and migration of breast cancer cells both invivo and invitro. However, verapamil, another calcium channel blocker, didn't exert the similar effects. Nifedipine and high concentration KCl failed to alter the [Ca2+]i in MDA-MB-231 cells, suggesting that such nifedipine effect was not related with calcium channel. Moreover, nifedipine decreased miRNA-524-5p, resulting in the up-regulation of brain protein I3 (BRI3). Erk pathway was consequently activated and led to the proliferation and migration of breast cancer cells. Silencing BRI3 reversed the promoting effect of nifedipine on the breast cancer. In a summary, nifedipine stimulated the proliferation and migration of breast cancer cells via the axis of miRNA-524-5p-BRI3-Erk pathway independently of its calcium channel-blocking activity. Our findings highlight that nifedipine but not verapamil is conducive for breast cancer growth and metastasis, urging that the caution should be taken in clinic to prescribe nifedipine to women who suffering both hypertension and breast cancer, and hypertension with a tendency in breast cancers.
authors.affiliation: Molecular Pharmacology Laboratory, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Dong-Qing
authors.initials: DQ
authors.lastname: Guo
authors.affiliation: Department of Surgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: The Department of Haematology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Sheng-Jiang
authors.initials: SJ
authors.lastname: Tan
authors.affiliation: Molecular Pharmacology Laboratory, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Gu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009543:Nifedipine / Q000008:administration & dosage* / Q000494:pharmacology; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: C499959:BRI3 protein, human; C000599909:MIRN-524 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D014700:Verapamil; D009543:Nifedipine