Silencing LPAATβ inhibits tumor growth of cisplatin-resistant human osteosarcoma in vivo and in vitro

Song,Lei; Duan,Ping; Gan,Yibo; Li,Pei; Zhao,Chen; Xu,Jianzhong; Zhang,Zehua; Zhou,Qiang

doi:10.3892/ijo.2016.3820

Silencing LPAATβ inhibits tumor growth of cisplatin-resistant human osteosarcoma in vivo and in vitro

Authors:
- Lei Song
- Ping Duan
- Yibo Gan
- Pei Li
- Chen Zhao
- Jianzhong Xu
- Zehua Zhang
- Qiang Zhou
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Affiliations: Department of Orthopaedics, First Affliated Hospital, Third Military Medical University, Chongqing 400038, P.R. China, Southwest Eye Hospital, First Affliated Hospital, Third Military Medical University, Chongqing 400038, P.R. China
Published online on: December 28, 2016 https://doi.org/10.3892/ijo.2016.3820
Pages: 535-544

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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.

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