Related Experiment Video
Updated: Jan 9, 2026
Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
Published on: April 3, 2018
Oncolytic Reovirus-Induced Prostaglandin E2 Production in Human Tumor Cells
Ikuho Ishigami1, Hiroaki Shimada2, Ayaka Ihara2
1Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, The University of Osaka, Osaka 565-0871, Japan.
Abstract:
Oncolytic viruses, which kill tumor cells by tumor cell-specific replication, elicit superior antitumor immunity by efficiently activating the innate immune system. However, innate immunity-mediated inflammation is an undesirable consequence that often induces cellular production of immunosuppressive cellular factors. Among various immunosuppressive cellular factors, much attention has recently been focused on prostaglandin E2 (PGE2). In this study, we examined PGE2 production in human tumor cells following treatment with the mammalian orthoreovirus type 3 Dearing strain (hereafter reovirus), which has been used as an oncolytic virus in preclinical and clinical studies. Reovirus significantly induced PGE2 secretion from several types of human tumor cells in a virus titer-dependent manner. A nuclear factor-kappa B (NF-κB) inhibitor, BAY11-7082, and a cyclooxygenase 2 (COX2) inhibitor, celecoxib, significantly inhibited PGE2 secretion, indicating that NF-κB and COX2 played a crucial role in reovirus-induced PGE2 production. Moreover, UV-irradiated reovirus (UV-Reo), which lost virus replication ability, did not increase PGE2 secretion. In addition, inhibitors of cathepsins B and L, cysteine lysosomal proteases crucial for reovirus replication, significantly reduced PGE2 secretion. These results indicate that reovirus replication in tumor cells is important for reovirus-induced PGE2 production. Attention should be paid to possible PGE2 production in tumors following reovirus treatment.
Insights
Oncolytic reovirus treatment significantly increases prostaglandin E2 (PGE2) production in human tumor cells. This PGE2 secretion is dependent on reovirus replication, involving nuclear factor-kappa B (NF-κB) and cyclooxygenase 2 (COX2) pathways.
Area of Science:
- Oncolytic virotherapy
- Immunology
- Cancer research
Background:
- Oncolytic viruses activate innate immunity for antitumor effects.
- Innate immunity can lead to immunosuppressive factors, such as prostaglandin E2 (PGE2).
- PGE2 is a key immunosuppressive factor implicated in tumor progression.
Purpose of the Study:
- To investigate prostaglandin E2 (PGE2) production in human tumor cells treated with mammalian orthoreovirus type 3 Dearing strain (reovirus).
- To elucidate the mechanisms underlying reovirus-induced PGE2 production.
Main Methods:
- Human tumor cells were treated with reovirus.
- PGE2 secretion was measured.
- Inhibitors of nuclear factor-kappa B (NF-κB), cyclooxygenase 2 (COX2), and cathepsins B/L were used.
- UV-inactivated reovirus (UV-Reo) was employed to assess replication dependence.
Main Results:
- Reovirus significantly induced PGE2 secretion in a virus titer-dependent manner.
- NF-κB and COX2 inhibitors substantially reduced PGE2 secretion.
- UV-Reo did not increase PGE2 secretion.
- Inhibitors of cathepsins B and L significantly reduced PGE2 secretion, highlighting the importance of reovirus replication.
Conclusions:
- Reovirus replication within tumor cells is essential for inducing PGE2 production.
- NF-κB and COX2 signaling pathways are critical for reovirus-mediated PGE2 secretion.
- Potential PGE2 production should be considered in reovirus-based cancer therapies.
