title: Knockdown of TRPM8 suppresses cancer malignancy and enhances epirubicin-induced apoptosis in human osteosarcoma cells.
abstract: As the function of transient receptor potential melastatin member 8 (TRPM8) in osteosarcoma is still unknown, we aim to investigate the possible effects and potential mechanisms of TRPM8 on cell proliferation, metastasis and chemosensitivity in osteosarcoma cells. We find that TRPM8 is aberrantly over-expressed in human osteosarcoma tissues and cell lines. Knockdown of TRPM8 by siRNA in osteosarcoma cells leads to the impaired regulation of intracellular Ca(2+) concentration and then the Akt-GSK-3β pathway and the phosphorylation of p44/p42 and FAK are suppressed. Knockdown of TRPM8 not only negatively influences the cell proliferation and metastasis but also enhances epirubicin-induced cell apoptosis. Such results reveal that TRPM8 is worthy further investigation for its potential as a clinical biomarker and therapeutic target in osteosarcoma.
authors.affiliation: Department of Urology, Zhongnan Hospital, Wuhan University, Wuhan, China, 430071.
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Urology, Zhongnan Hospital, Wuhan University, Wuhan, China, 430071.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Urology, Zhongnan Hospital, Wuhan University, Wuhan, China, 430071.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Meng
authors.affiliation: Department of Urology, Zhongnan Hospital, Wuhan University, Wuhan, China, 430071.
authors.forename: Hong
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Urology, Zhongnan Hospital, Wuhan University, Wuhan, China, 430071.
authors.forename: Guangbin
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Department of Urology, Zhongnan Hospital, Wuhan University, Wuhan, China, 430071.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Urology, Zhongnan Hospital, Wuhan University, Wuhan, China, 430071.
authors.forename: Xinghuan
authors.initials: X
authors.lastname: Wang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015251:Epirubicin / Q000494:pharmacology*; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; D034741:RNA, Small Interfering; D050053:TRPM Cation Channels; C425966:TRPM8 protein, human; D015251:Epirubicin; D011494:Protein Kinases; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D002118:Calcium
keywords: MAPK; TRPM8; apoptosis; epirubicin; osteosarcoma