Cisplatin-resistant HepG2 cell-derived exosomes transfer cisplatin resistance to cisplatin-sensitive cells in HCC.
Cell viability
Drug resistance
Journal
PeerJ
ISSN: 2167-8359
Titre abrégé: PeerJ
Pays: United States
ID NLM: 101603425
Informations de publication
Date de publication:
2021
2021
Historique:
received:
21
12
2020
accepted:
10
03
2021
entrez:
6
5
2021
pubmed:
7
5
2021
medline:
7
5
2021
Statut:
epublish
Résumé
Cancer cell resistance to chemotherapy drugs such as Gemcitabine, Oxaliplatin, Cisplatin, Doxorubicin, and 5-fluorouracil account for the main reason of chemotherapy failure for HCC patients, especially for those with advanced HCC or metastasis patients. This emerging resistance limits the effectiveness and clinical application of these chemotherapy drugs. Previous studies reported that drug-resistant tumor cell-derived exosomes could transfer their resistance property to tumor sensitive cells in some cancer, including lung and gastric cancer. This study sought to explore whether HepG2/DDP cell-derived exosomes transmit cisplatin (DDP) resistance to HepG2 and other HCC sensitive cells, and provide considerable guidance for HCC nursing with Cisplatin DDP clinically. The HepG2 DDP-resistant cell line (HepG2/DDP) was established, and the exosomes from both HepG2/DDP and HepG2 cells were isolated and named ES-2, ES-1, respectively. HepG2 or SMMC-7721 or Huh7 cells were treated with DDP or DDP + ES-2, and HepG2/DDP cells were treated with ES-1. Then, the activation of drug resistance via HepG2/DDP exosomes transfer to HepG2, SMMC-7721 and Huh7 cells were assessed by cell viability assay and ROS formation. Moreover, the relative expression of P-glycoprotein (P-gp) was measured by western blot analysis. HepG2/DDP cell-derived exosomes were successfully isolated from cisplatin-resistant HepG2 cells, and named ES-2. Cell viability of HepG2 or SMMC-7721 or Huh7 cells treated with DDP + ES-2 was enhanced compared with that of DDP treatment group. Also, the concentration of ROS generated in cells under DDP or DDP + ES-2 treatment was strongly increased compared with that of control, although the concentration of ROS was clearly smaller in DDP + ES-2 treatment group compared with DDP treatment. At the same time, the expression of P-gp was upregulated on the ES-2 surface. The results mentioned above clarified that HepG2/DDP cell-derived exosomes conferred cisplatin resistance to HepG2 and other HCC cell lines, and provided a new significance for improving the effectiveness of DDP in treating HCC.
Sections du résumé
BACKGROUNDS
BACKGROUND
Cancer cell resistance to chemotherapy drugs such as Gemcitabine, Oxaliplatin, Cisplatin, Doxorubicin, and 5-fluorouracil account for the main reason of chemotherapy failure for HCC patients, especially for those with advanced HCC or metastasis patients. This emerging resistance limits the effectiveness and clinical application of these chemotherapy drugs. Previous studies reported that drug-resistant tumor cell-derived exosomes could transfer their resistance property to tumor sensitive cells in some cancer, including lung and gastric cancer. This study sought to explore whether HepG2/DDP cell-derived exosomes transmit cisplatin (DDP) resistance to HepG2 and other HCC sensitive cells, and provide considerable guidance for HCC nursing with Cisplatin DDP clinically.
METHODS
METHODS
The HepG2 DDP-resistant cell line (HepG2/DDP) was established, and the exosomes from both HepG2/DDP and HepG2 cells were isolated and named ES-2, ES-1, respectively. HepG2 or SMMC-7721 or Huh7 cells were treated with DDP or DDP + ES-2, and HepG2/DDP cells were treated with ES-1. Then, the activation of drug resistance via HepG2/DDP exosomes transfer to HepG2, SMMC-7721 and Huh7 cells were assessed by cell viability assay and ROS formation. Moreover, the relative expression of P-glycoprotein (P-gp) was measured by western blot analysis.
RESULTS
RESULTS
HepG2/DDP cell-derived exosomes were successfully isolated from cisplatin-resistant HepG2 cells, and named ES-2. Cell viability of HepG2 or SMMC-7721 or Huh7 cells treated with DDP + ES-2 was enhanced compared with that of DDP treatment group. Also, the concentration of ROS generated in cells under DDP or DDP + ES-2 treatment was strongly increased compared with that of control, although the concentration of ROS was clearly smaller in DDP + ES-2 treatment group compared with DDP treatment. At the same time, the expression of P-gp was upregulated on the ES-2 surface.
CONCLUSION
CONCLUSIONS
The results mentioned above clarified that HepG2/DDP cell-derived exosomes conferred cisplatin resistance to HepG2 and other HCC cell lines, and provided a new significance for improving the effectiveness of DDP in treating HCC.
Identifiants
pubmed: 33954040
doi: 10.7717/peerj.11200
pii: 11200
pmc: PMC8051335
doi:
Banques de données
figshare
['10.6084/m9.figshare.13442978.v1']
Types de publication
Journal Article
Langues
eng
Pagination
e11200Informations de copyright
©2021 Tang et al.
Déclaration de conflit d'intérêts
The authors declare there are no competing interests.
Références
Nanomedicine (Lond). 2017 Sep;12(17):2137-2148
pubmed: 28805111
Semin Cell Dev Biol. 2018 Jun;78:3-12
pubmed: 28751251
Nucleic Acids Res. 2012 Sep 1;40(17):e130
pubmed: 22618874
Hepatology. 2016 Jul;64(1):106-16
pubmed: 26765068
J Surg Oncol. 2017 Jun;115(8):932-940
pubmed: 28334432
Mol Cancer Ther. 2005 Oct;4(10):1595-604
pubmed: 16227410
Genomics Proteomics Bioinformatics. 2015 Feb;13(1):17-24
pubmed: 25724326
N Engl J Med. 2011 Sep 22;365(12):1118-27
pubmed: 21992124
Cancers (Basel). 2016 Dec 09;8(12):
pubmed: 27941677
World J Hepatol. 2015 Jun 28;7(12):1632-51
pubmed: 26140083
Int J Nanomedicine. 2017 May 15;12:3721-3733
pubmed: 28553110
Curr Opin Oncol. 2013 Jan;25(1):66-75
pubmed: 23165142
Clin Liver Dis. 2015 May;19(2):421-32
pubmed: 25921671
J Exp Clin Cancer Res. 2016 Sep 30;35(1):159
pubmed: 27716356
PLoS One. 2012;7(12):e50999
pubmed: 23251413
Drug Metab Rev. 2003 Nov;35(4):417-54
pubmed: 14705869
J Exp Clin Cancer Res. 2016 Jun 27;35:103
pubmed: 27349385
Nat Commun. 2018 Feb 8;9(1):562
pubmed: 29422620
Br J Cancer. 2003 Apr 22;88(8):1327-34
pubmed: 12698203
Nat Rev Clin Oncol. 2015 Jul;12(7):408-24
pubmed: 26054909
CA Cancer J Clin. 2015 Mar;65(2):87-108
pubmed: 25651787