title: Silencing LPAATβ inhibits tumor growth of cisplatin-resistant human osteosarcoma in vivo and in vitro.
abstract: Cisplatin-resistance has become a major impediment in the medical treatment of cancers such as osteosarcoma, the most common primary malignancy of bone. Since lysophosphatidic acid acyltransferase β (LPAATβ) was reported to be critically involved in osteosarcoma, our study investigated the role of LPAATβ in human osteosarcoma with cisplatin-resistance. Expression of LPAATβ or other relevant proteins were analyzed in 40 osteosarcoma patients by immunohistochemistry analysis (IHC), and in cisplatin‑resistant sublines by real-time PCR and western blotting. Next, the synthesized siRNA was inserted into the lentivirus vector and silencing of LPAATβ expression was employed to determine the effect of LPAATβ on cisplatin-resistant osteosarcoma cell viability in vitro and osteosarcoma tumor growth in vivo with cisplatin treatment. Exogenous LPAATβ mediated by heritable RNAi decreased cisplatin‑resistant sensitivity through activating the PI3K/Akt/mTOR signaling pathway. We further demonstrate that silencing LPAATβ effectively inhibited tumor growth in nude mice with xenografts of cisplatin‑resistant osteosarcoma cells. IHC assay results showed that PI3K/Akt/mTOR signaling pathway was also involved in this process. Our results suggested that LPAATβ may play an important role in osteosarcoma and silencing LPAATβ may be exploited as a novel therapeutic strategy for the clinical management of cisplatin-resistance.
authors.affiliation: Department of Orthopaedics, First Affliated Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.affiliation: Southwest Eye Hospital, First Affliated Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Duan
authors.affiliation: Department of Orthopaedics, First Affliated Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Gan
authors.affiliation: Department of Orthopaedics, First Affliated Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Pei
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, First Affliated Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedics, First Affliated Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Orthopaedics, First Affliated Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Zehua
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, First Affliated Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000217:Acyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D055815:Young Adult
chemical_list: D034741:RNA, Small Interfering; D000217:Acyltransferases; C018764:2-acylglycerophosphate acyltransferase; D002945:Cisplatin