Targeting proteasome enhances anticancer activity of oncolytic HSV-1 in colorectal cancer

  • Virology. 2023 Jan:578:13-21. doi: 10.1016/j.virol.2022.11.002.
Xiaxi Li  1 ,  Wei Hu  1 ,  Jiangang Shen  2 ,  Mingsong Li  3 ,  Wei Gong  4
Affiliations
  • 1. Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China.
  • 2. Department of Gastroenterology, People's Hospital of Longhua District of Shenzhen, Shenzhen, Guangdong, China.
  • 3. Department of Gastroenterology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. Electronic address: [email protected].
  • 4. Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China. Electronic address: [email protected].
PMID: 36434905 DOI: 10.1016/j.virol.2022.11.002
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.

Keywords
Bortezomib; Colorectal cancer cells; Drug combination; HSV-1; Oncolysis.
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