title: Procaine Inhibits Proliferation and Migration and Promotes Cell Apoptosis in Osteosarcoma Cells by Upregulation of MicroRNA-133b.
abstract: Procaine (PCA) is a conventional chemotherapeutic agent for osteosarcoma. Recent studies have proposed that the growth-inhibitory effect of PCA is through regulation of microRNAs (miRNAs). miR-133b has been proven to be a tumor suppressor in osteosarcoma, but whether it is involved in the antitumor effects of PCA on osteosarcoma has not been investigated. In this study, we aimed to explore the effects of PCA on osteosarcoma MG63 cells by regulation of miR-133b, as well as its underlying mechanisms. MG63 cells were treated with different concentrations of PCA, and cell viability, apoptosis, and miR-133b expression were then detected by MTT, flow cytometry, and qRT-PCR, respectively. Cells were then transfected with the miR-133b inhibitor and treated with 2 μM PCA. Thereafter, cell viability, migration, and apoptosis were detected. Analysis of signaling pathways was detected by Western blot. Our results showed that PCA significantly inhibited cell viability and promoted apoptosis and the expression level of miR-133b in a dose-dependent manner (p < 0.05 or p < 0.01). Moreover, we observed that PCA + miR-133b inhibitor dramatically reversed the effects of PCA on cell viability, apoptosis, and migration (p < 0.05 or p < 0.01). In addition, PCA significantly decreased the levels of p/t-AKT (p308 or p473), p/t-ERK, and p/t-S6, whereas PCA + miR-133b inhibitor rescued these effects. Our results suggest that PCA inhibits proliferation and migration but promotes apoptosis in osteosarcoma cells by upregulation of miR-133b. These effects may be achieved by inactivation of the AKT/ERK pathways.
authors.forename: Boda
authors.initials: B
authors.lastname: Ying
authors.forename: Hong
authors.initials: H
authors.lastname: Huang
authors.forename: Hongfei
authors.initials: H
authors.lastname: Li
authors.forename: Meng
authors.initials: M
authors.lastname: Song
authors.forename: Sizhan
authors.initials: S
authors.lastname: Wu
authors.forename: Hongliang
authors.initials: H
authors.lastname: Ying
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D012516:Osteosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011343:Procaine / Q000494:pharmacology*; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000779:Anesthetics, Local; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D011343:Procaine