PMID- 32742448
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 1837-9664 (Print)
IS  - 1837-9664 (Electronic)
IS  - 1837-9664 (Linking)
VI  - 11
IP  - 17
DP  - 2020
TI  - Graphene Oxide Nanoparticles Induce Apoptosis in wild-type and 
      CRISPR/Cas9-IGF/IGFBP3 knocked-out Osteosarcoma Cells.
PG  - 5007-5023
LID - 10.7150/jca.46464 [doi]
AB  - Osteosarcoma affects both adolescents and adults, and some improvement in the 
      survival rate for affected patients has been reached in the last decade. Still, 
      non-specificity and systemic toxicity may limit traditional therapeutic 
      approaches to some extent. The insulin growth factor 1 (IGF1) and its binding 
      protein (IGFBP3) have been implicated in the tumorigenesis. Nanoparticles, such 
      as graphene oxide (GO), can provide an effective treatment for cancer as they can 
      specifically target cancer cells while reducing undesired side effects. This 
      study aimed to evaluate the toxicity of GO on osteosarcoma in vitro using tumor 
      cell lines with and without knocking out the IGF and IGFBP3 genes. Human 
      osteosarcoma cell lines, U2OS and SAOS2, and the normal osteoblast cell line 
      hFOB1.19 were used. The IGF1 and IGFBP3 genes were eliminated using CRISPR/Cas9. 
      Tumor cells were cultured and treated with GO. Apoptosis and reactive oxygen 
      species (ROS) were analyzed by Annexin V-FITC and ROS assays. The nuclear factor 
      erythroid 2-related factor 2 (NRF2), which is a crucial regulator of cellular 
      resistance to oxidants, was investigated by Western blotting. We found a 
      significantly higher rate of apoptosis in the OS than hFOB1.19, especially in 
      U2OS cells in which IGF1 and IGFBP3 were knocked out. ROS increase due to GO 
      exposure was remarkably time and concentration-dependent. Based on the rate of 
      apoptosis, ROS, Nrf-2 decrease, and cytomorphological changes, GO has a 
      significant cytotoxic effect against OS. Targeting the IGF1 and IGFBP3 signaling 
      pathway may strengthen GO-related cytotoxicity with the potential to increase the 
      survival of patients affected by this tumor.
CI  - (c) The author(s).
FAU - Burnett, Mervin
AU  - Burnett M
AD  - Department of Laboratory Medicine and Pathology, Stollery Children's Hospital, 
      University of Alberta, Edmonton, Alberta, Canada.
FAU - Abuetabh, Yasser
AU  - Abuetabh Y
AD  - Department of Laboratory Medicine and Pathology, Heritage Medical Research 
      Centre, University of Alberta, Edmonton, Alberta, Canada.
FAU - Wronski, Ania
AU  - Wronski A
AD  - Synthego Corporation, Menlo Park, CA 94025, USA.
FAU - Shen, Fan
AU  - Shen F
AD  - Department of Laboratory Medicine and Pathology, Stollery Children's Hospital, 
      University of Alberta, Edmonton, Alberta, Canada.
FAU - Persad, Sujata
AU  - Persad S
AD  - Department of Paediatrics, University of Alberta, Edmonton, Alberta, Canada.
FAU - Leng, Roger
AU  - Leng R
AD  - Department of Laboratory Medicine and Pathology, Heritage Medical Research 
      Centre, University of Alberta, Edmonton, Alberta, Canada.
FAU - Eisenstat, David
AU  - Eisenstat D
AD  - Department of Paediatrics, University of Alberta, Edmonton, Alberta, Canada.
AD  - Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.
AD  - Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
FAU - Sergi, Consolato
AU  - Sergi C
AD  - Department of Laboratory Medicine and Pathology, Stollery Children's Hospital, 
      University of Alberta, Edmonton, Alberta, Canada.
AD  - Department of Paediatrics, University of Alberta, Edmonton, Alberta, Canada.
AD  - National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key 
      Laboratory of Fermentation Engineering (Ministry of Education), Hubei University 
      of Technology, Wuhan 430068, P.R. China.
AD  - Department of Orthopedics, Tianyou Hospital, Wuhan University of Science and 
      Technology, Wuhan, Hubei, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20200621
PL  - Australia
TA  - J Cancer
JT  - Journal of Cancer
JID - 101535920
PMC - PMC7378933
OTO - NOTNLM
OT  - Graphene oxide
OT  - IGF1
OT  - IGFBP3
OT  - Osteosarcoma
OT  - ROS, CRISPR-Cas9
OT  - apoptosis
OT  - cell line
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2020/08/04 06:00
MHDA- 2020/08/04 06:01
PMCR- 2020/01/01
CRDT- 2020/08/04 06:00
PHST- 2020/03/29 00:00 [received]
PHST- 2020/06/09 00:00 [accepted]
PHST- 2020/08/04 06:00 [entrez]
PHST- 2020/08/04 06:00 [pubmed]
PHST- 2020/08/04 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - jcav11p5007 [pii]
AID - 10.7150/jca.46464 [doi]
PST - epublish
SO  - J Cancer. 2020 Jun 21;11(17):5007-5023. doi: 10.7150/jca.46464. eCollection 2020.