Targeting proteasome enhances anticancer activity of oncolytic HSV-1 in colorectal cancer.
Virology
; 578: 13-21, 2023 01.
Article
em En
| MEDLINE
| ID: mdl-36434905
ABSTRACT
Herpes simplex virus 1 (HSV-1) has been widely used to treat various cancers, but its efficacy is limited. Studies indicated that combining HSV-1 and chemotherapy drugs can effectively improve the lethality of HSV-1 in tumor cells, which has a synergistic effect. Here, we explored the oncolytic effect and mechanism of bortezomib and HSV-1 on colorectal cancer cells, HCT116 and Caco-2. First, we selected four drugs to detect cell viability and found that the strongest HSV-1-promoting effect was achieved using bortezomib + HSV-1 treatment. Bortezomib combined with HSV-1 treatment significantly upregulated the expression of heat shock proteins, endoplasmic reticulum stress-related proteins and apoptosis-related proteins, while Bcl-2 was downregulated. JC-1 staining revealed that combining bortezomib and HSV-1 promotes cell apoptosis. In addition, bortezomib + oHSV-1 treatment effectively inhibit tumor growth. These results indicate that bortezomib combined with HSV-1 induce intense endoplasmic reticulum stress and activate the caspase-12 apoptosis pathway, killing tumor cells.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Herpesvirus Humano 1
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Terapia Viral Oncolítica
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article