TGM2 knockdown reverses cisplatin chemoresistance in osteosarcoma

Li,Cuiyun; Cai,Jing; Ge,Fugui; Wang,Guilong

doi:10.3892/ijmm.2018.3753

TGM2 knockdown reverses cisplatin chemoresistance in osteosarcoma

Authors:
- Cuiyun Li
- Jing Cai
- Fugui Ge
- Guilong Wang
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Affiliations: Department of Pathology, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China, Department of Neurosurgery, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China, Department of Surgery, Linyi Women's and Children's Hospital, Linyi, Shandong 276000, P.R. China, Department of Orthopedics, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China
Published online on: July 4, 2018 https://doi.org/10.3892/ijmm.2018.3753
Pages: 1799-1808
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In the past decades, chemotherapy has resulted in improved outcomes for patients with osteosarcoma. However, resistance to chemotherapy often leads to poor prognoses. Cisplatin is a standard drug for osteosarcoma therapy, and chemoresistance to cisplatin in osteosarcoma limits the effectiveness of chemotherapy drugs. Transglutaminase 2 (TGM2) is a member of the transglutaminase family, and it is reported to be associated with chemoresistance in various types of cancer. The present study aimed to investigate the function of TGM2 in regulating chemosensitivity of osteosarcoma cells to cisplatin. For in vitro experiments, a cisplatin‑resistant osteosarcoma cell line (Saos2‑CIS‑R) was established, and TGM2 was demonstrated to be upregulated in the resistant Saos2‑CIS‑R cells compared with the normal Saos2 cells. The present study also revealed that TGM2 was associated with chemoresistance to cisplatin in osteosarcoma cells, and knockdown of TGM2 enhanced their chemosensitivity. In addition, TGM2 was demonstrated to affect the chemosensitivity of osteosarcoma cells via regulation of the activation of mitogen‑activated protein kinase and AKT serine/threonine kinase pathways. Expression of BCL2 apoptosis regulator, BCL2 associated X and caspase‑3 was also involved in chemoresistance development in osteosarcoma. For in vivo experiments, a mouse model was used to detect that the cisplatin sensitivity of Saos2‑CIS‑R cells was reversed following TGM2 knockdown. Taken together, the present data suggested a potentially important role for TGM2 in the regulation of osteosarcoma chemosensitivity. TGM2 might therefore serve as a therapeutic target for osteosarcoma.

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