title: CXCR1 knockdown improves the sensitivity of osteosarcoma to cisplatin.
abstract: Chemotherapy resistance is a major cause of poor prognoses for osteosarcoma patients. This study aimed to determine whether CXCR1 gene knockdown improves the sensitivity of osteosarcomas to chemotherapy. Both CXCR1 expression and cisplatin sensitivity were investigated and compared in two osteosarcoma cell lines. Sensitivity to the chemotherapy drug cisplatin and apoptosis were investigated with or without stimulation via Interleukin-8 (IL-8), which is a ligand of CXCR1. Furthermore, activation of the Akt signaling pathway was determined. Finally, luciferase-labeled CXCR1-knockdown Saos2-lung cells were injected into the tibiae of nude mice that were treated with cisplatin thereafter. We found that CXCR1 expression and cisplatin sensitivity were negatively correlated in osteosarcoma cell lines. IL-8-induced reduction in sensitivity could be blocked by silencing CXCR1, and CXCR1 knockdown suppressed the Akt signaling pathway. Moreover, CXCR1-knockdown tumors were significantly smaller than control tumors, which was consistent with the luciferase intensity results. The expression levels of IL-8, CXCR1 and p-Akt were suppressed in CXCR1-knockdown cells. Taken together, these data indicate that CXCR1 gene knockdown in osteosarcoma cells improved the sensitivity to chemotherapy and that this process might be regulated in part by the IL-8/CXCR1/Akt signaling pathway.
authors.affiliation: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xiu-guo
authors.initials: XG
authors.lastname: Han
authors.affiliation: Department of Orthopedic Surgery, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Du
authors.affiliation: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Han
authors.initials: H
authors.lastname: Qiao
authors.affiliation: Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Tu
authors.affiliation: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yu-gang
authors.initials: YG
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: An
authors.initials: A
authors.lastname: Qin
authors.affiliation: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ke-rong
authors.initials: KR
authors.lastname: Dai
authors.affiliation: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: chillow@163.com.
authors.forename: Qi-ming
authors.initials: QM
authors.lastname: Fan
authors.affiliation: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: tingtingtang@hotmail.com.
authors.forename: Ting-ting
authors.initials: TT
authors.lastname: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D016209:Interleukin-8; D023062:Receptors, Interleukin-8A; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin
keywords: Akt signaling pathway; CXCR1 silencing; Cisplatin sensitivity; Interleukin-8; Osteosarcoma