ONCOLYTIC ACTIVITY OF HUMAN ORTHOPNEUMOVIRUS IN CANCER CELL LINES

Authors

  • I.M. Aziz College of Science, King Saud University, Riyadh 11451, Saudi Arabia
  • R. Bhat College of Science, King Saud University, Riyadh 11451, Saudi Arabia
  • M.A. Farrag College of Science, King Saud University, Riyadh 11451, Saudi Arabia
  • F.N. Almajhdi College of Science, King Saud University, Riyadh 11451, Saudi Arabia

DOI:

https://doi.org/10.32471/exp-oncology.2312-8852.vol-44-no-2.18084

Keywords:

human orthopneumovirus, immune activation, immunotherapy, oncolytic virotherapy, oncolytic viruses, tumors

Abstract

Oncolytic virotherapy is an emerging biotherapeutic platform for selectively infecting cancer cells and triggering apoptosis in a number of malignant cells due to robust viral replication. Studies related to the oncolytic activity of human orthopneumovirus (hOPV) are conflicting. Aim: This study was designed to elucidate the possible role of hOPV in the modulation of cell growth and apoptosis in cancer cell lines including human epidermoid carcinoma (HEp-2), lung epithelial cell line (A549), and breast cancer cell line (MCF-7). Materials and Methods: The oncolytic activity of hOPV on cancer cells was studied in vitro. The virus titers were determined by tissue culture infectious dose (TCID50/mL) in A549 cell. The cytotoxic effect of the virus on HEp-2, A549, and MCF-7 was determined using MTT and trypan blue dye exclusion test assays. hOPV in the infected cells was detected using real-time reverse transcription polymerase chain reaction (rRT-PCR) and indirect immunofluorescence (IIF) assays. The relative expression of apoptosis-related genes (CASP-3, -8, -9, Bax, Bcl-2, Bcl-XL, TP53, P21) during virus infection was estimated using rRT-PCR assay in comparison with the house-keeping gene (GAPDH). Results: hOPV infection inhibited the growth of HEp-2, A549, and MCF-7 cells in a dose-and time-dependent manner. At a multiplicity of infection (MOI) of 5, hOPV reduced the viability of A549 cells to about 16%, HEp-2 to 22%, and MCF-7 to 28% (p = 0.001), while no significant inhibitory effect was observed when cells were infected at MOI of 1 and 2. hOPV mRNA and antigens were detected in infected HEp-2, A549, and MCF-7 cells by RT-PCR and IIF. Upon hOPV infection, expression of CASP-3, -8, -9, as well as Bax, TP53, and p21 mRNA increased while expression of Bcl-2, Bcl-xL anti-apoptotic genes decreased. In hOPV-infected A549 cells, the fold increase of CASP-8 and CASP-9, Bax, TP53, and P21 expression exceeded significantly compared to that in HEp-2 or MCF-7 cells. Conclusions: Our results provide evidence that hOPV could be a potential candidate for oncolytic virotherapy.

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Published

26.05.2023

How to Cite

Aziz, I., Bhat, R., Farrag, M., & Almajhdi, F. (2023). ONCOLYTIC ACTIVITY OF HUMAN ORTHOPNEUMOVIRUS IN CANCER CELL LINES. Experimental Oncology, 44(2), 113–120. https://doi.org/10.32471/exp-oncology.2312-8852.vol-44-no-2.18084

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