Cell type-specific response of colon cancer tumor cell lines to oncolytic HSV-1 virotherapy in hypoxia.
CRC
HMGB1
Hypoxia
Normoxia
Oncolytic herpes virus type1
oHSV-1
Journal
Cancer cell international
ISSN: 1475-2867
Titre abrégé: Cancer Cell Int
Pays: England
ID NLM: 101139795
Informations de publication
Date de publication:
27 Apr 2022
27 Apr 2022
Historique:
received:
19
11
2021
accepted:
29
03
2022
entrez:
28
4
2022
pubmed:
29
4
2022
medline:
29
4
2022
Statut:
epublish
Résumé
Novel strategies are required since the hypoxic tumor microenvironment is one of the important impediments for conventional cancer therapy. High mobility group box 1 (HMGB1) protein can block aerobic respiration in cancer cells. We hypothesized that HMGB1could also kill the colorectal cancer cells during hypoxia. In this study, we developed oncolytic herpes simplex virus type 1 expressing HMGB1 protein (HSV-HMGB1) and investigated the cytotoxic effect of HSV-HMGB1 and its parental virus (HSV-ble) on three colorectal cancer cells (HCT116, SW480, and HT29) under normoxic (20% oxygen) and hypoxic (1% oxygen) conditions. We further identified potential autophagy- related genes in HT29 cells by retrieving mRNA expression microarray datasets from the Gene Expression Omnibus database. These genes were then detected in HT29 cells infected with HSV-HMGB1 and HSV-ble during normoxia and hypoxia by Real-Time quantitative PCR (qRT-PCR). The cytotoxic effect of HSV-HMGB1 was significantly higher than that of HSV-ble during normoxia; however, during hypoxia, HSV-HMGB1 enhanced the viability of HT29 cells at MOI 0.1. Analyzing the cell death pathway revealed that HSV-HMGB1 induced autophagy in HT29 cells under hypoxic conditions. In conclusion, it appears that oncolytic virotherapy is cell context-dependent. Therefore, understanding the cancer cells' characteristics, microenvironment, and cell signaling are essential to improve the therapeutic strategies.
Sections du résumé
BACKGROUND
BACKGROUND
Novel strategies are required since the hypoxic tumor microenvironment is one of the important impediments for conventional cancer therapy. High mobility group box 1 (HMGB1) protein can block aerobic respiration in cancer cells. We hypothesized that HMGB1could also kill the colorectal cancer cells during hypoxia.
METHODS
METHODS
In this study, we developed oncolytic herpes simplex virus type 1 expressing HMGB1 protein (HSV-HMGB1) and investigated the cytotoxic effect of HSV-HMGB1 and its parental virus (HSV-ble) on three colorectal cancer cells (HCT116, SW480, and HT29) under normoxic (20% oxygen) and hypoxic (1% oxygen) conditions. We further identified potential autophagy- related genes in HT29 cells by retrieving mRNA expression microarray datasets from the Gene Expression Omnibus database. These genes were then detected in HT29 cells infected with HSV-HMGB1 and HSV-ble during normoxia and hypoxia by Real-Time quantitative PCR (qRT-PCR).
RESULTS
RESULTS
The cytotoxic effect of HSV-HMGB1 was significantly higher than that of HSV-ble during normoxia; however, during hypoxia, HSV-HMGB1 enhanced the viability of HT29 cells at MOI 0.1. Analyzing the cell death pathway revealed that HSV-HMGB1 induced autophagy in HT29 cells under hypoxic conditions.
CONCLUSION
CONCLUSIONS
In conclusion, it appears that oncolytic virotherapy is cell context-dependent. Therefore, understanding the cancer cells' characteristics, microenvironment, and cell signaling are essential to improve the therapeutic strategies.
Identifiants
pubmed: 35477503
doi: 10.1186/s12935-022-02564-4
pii: 10.1186/s12935-022-02564-4
pmc: PMC9044800
doi:
Types de publication
Journal Article
Langues
eng
Pagination
164Subventions
Organisme : National Institute for Medical Research Development
ID : 958916
Informations de copyright
© 2022. The Author(s).
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