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TGM2 knockdown reverses cisplatin chemoresistance in osteosarcoma.

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 c... Full description

Journal Title: International journal of molecular medicine October 2018, Vol.42(4), pp.1799-1808
Main Author: Li, Cuiyun
Other Authors: Cai, Jing , Ge, Fugui , Wang, Guilong
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1791-244X ; DOI: 10.3892/ijmm.2018.3753
Link: http://search.proquest.com/docview/2071572676/?pq-origsite=primo
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recordid: proquest2071572676
title: TGM2 knockdown reverses cisplatin chemoresistance in osteosarcoma.
format: Article
creator:
  • Li, Cuiyun
  • Cai, Jing
  • Ge, Fugui
  • Wang, Guilong
subjects:
  • Bone Neoplasms–Drug Therapy
  • Cell Line, Tumor–Genetics
  • Cisplatin–Metabolism
  • Drug Resistance, Neoplasm–Pathology
  • Gtp-Binding Proteins–Pharmacology
  • Gene Knockdown Techniques–Drug Effects
  • Genes, Neoplasm–Genetics
  • Humans–Genetics
  • Neoplasm Proteins–Metabolism
  • Osteosarcoma–Genetics
  • Signal Transduction–Metabolism
  • Transglutaminases–Drug Therapy
  • Transglutaminases–Genetics
  • Transglutaminases–Metabolism
  • Transglutaminases–Pathology
  • Transglutaminases–Drug Effects
  • Transglutaminases–Genetics
  • Transglutaminases–Genetics
  • Transglutaminases–Metabolism
  • Neoplasm Proteins
ispartof: International journal of molecular medicine, October 2018, Vol.42(4), pp.1799-1808
description: 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.
language: eng
source:
identifier: E-ISSN: 1791-244X ; DOI: 10.3892/ijmm.2018.3753
fulltext: fulltext
issn:
  • 1791244X
  • 1791-244X
url: Link


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titleTGM2 knockdown reverses cisplatin chemoresistance in osteosarcoma.
creatorLi, Cuiyun ; Cai, Jing ; Ge, Fugui ; Wang, Guilong
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ispartofInternational journal of molecular medicine, October 2018, Vol.42(4), pp.1799-1808
identifierE-ISSN: 1791-244X ; DOI: 10.3892/ijmm.2018.3753
subjectBone Neoplasms–Drug Therapy ; Cell Line, Tumor–Genetics ; Cisplatin–Metabolism ; Drug Resistance, Neoplasm–Pathology ; Gtp-Binding Proteins–Pharmacology ; Gene Knockdown Techniques–Drug Effects ; Genes, Neoplasm–Genetics ; Humans–Genetics ; Neoplasm Proteins–Metabolism ; Osteosarcoma–Genetics ; Signal Transduction–Metabolism ; Transglutaminases–Drug Therapy ; Transglutaminases–Genetics ; Transglutaminases–Metabolism ; Transglutaminases–Pathology ; Transglutaminases–Drug Effects ; Transglutaminases–Genetics ; Transglutaminases–Genetics ; Transglutaminases–Metabolism ; Neoplasm Proteins
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descriptionIn 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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