title: Quercetin Enhances Cisplatin Sensitivity of Human Osteosarcoma Cells by Modulating microRNA-217-KRAS Axis.
abstract: Quercetin can suppress osteosarcoma cell growth and metastasis. However, other effects of quercetin on osteosarcoma remain largely unknown. This research aims to evaluate the effects of quercetin in combination with cisplatin as treatment for osteosarcoma and investigate its regulatory mechanism. Cell viability and apoptosis in 143B cell line were determined after treatment with quercetin and/or cisplatin. RT-PCR and Western blot analysis were performed to determine the RNA or protein expression levels. Moreover, transwell assay was used to evaluate metastasis. Furthermore, rescue experiments were performed to investigate the potential regulatory mechanism of the treatment. Results showed that quercetin with concentration that was equal to or greater than 10 μM inhibited 143B proliferation, while 5 μM quercetin enhanced the cisplatin sensitivity of 143B cells. Expression of miR-217 was upregulated after quercetin and/or cisplatin treatment, while its target KRAS was downregulated both at mRNA and protein levels. MiR-217 knockdown led to the loss of enhanced cisplatin sensitivity while miR-217 overexpression showed the opposite effects, indicating that quercetin regulated cisplatin sensitivity by modulating the miR-217-KRAS axis. In conclusion, 5 μM quercetin enhanced the cisplatin sensitivity by modulating the miR-217-KRAS axis. This finding suggests that quercetin may be administered with cisplatin to improve the treatment for osteosarcoma.
authors.affiliation: Department of Orthopaedics, the First Hospital Affiliated of Henan University, Henan, 475000, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, the First Hospital Affiliated of Henan University, Henan, 475000, China.
authors.forename: Qinggong
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Orthopaedics, the First Hospital Affiliated of Henan University, Henan, 475000, China.
authors.forename: Jingtao
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, the First Hospital Affiliated of Henan University, Henan, 475000, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000378:metabolism*; D004351:Drug Resistance / Q000187:drug effects*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D012516:Osteosarcoma / Q000188:drug therapy*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*
chemical_list: C117307:KRAS protein, human; C553315:MIRN217 microRNA, human; D035683:MicroRNAs; D011794:Quercetin; D016283:Proto-Oncogene Proteins p21(ras); D002945:Cisplatin
keywords: KRAS; cisplatin; microRNA-217; osteosarcoma; quercetin