Cell type-specific response of colon cancer tumor cell lines to oncolytic HSV-1 virotherapy in hypoxia

Cancer Cell International

Asghar Abdoli¹  Golnaz Bahramali¹  Mohammad Sadegh Shams Nosrati²  Sara Shayan²  Kayhan Azadmanesh²  Arash Arashkia² 

[1] Department of Hepatitis and AIDS and Blood Borne Diseases, Pasteur Institute of Iran;Department of Molecular Virology, Pasteur Institute of Iran;

关键词: Oncolytic herpes virus type1;    oHSV-1;    HMGB1;    CRC;    Hypoxia;    Normoxia;   

DOI  :  10.1186/s12935-022-02564-4

来源: DOAJ

【 摘 要 】

Abstract 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 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 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 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.

【 授权许可】

Unknown