Abstract
BackgroundOncolytic viruses have emerged as an alternative therapeutic modality for cancer as they can replicate specifically in tumour cells and induce toxic effects leading to apoptosis. Despite the great potentials and promising results shown in multiple studies, it appears that their efficacy is still moderate and deemed as not sufficient in clinical studies. In addressing this issue, genetic/molecular engineering approach has paved its way to improve the therapeutic efficacy as observed in the case of herpes simplex virus (HSV) expressing granulocyte–macrophage colony-stimulating factor (GM-CSF). This study aimed to explore the cytotoxicity effects of recombinant NDV strain AF2240-i expressing interleukin-12 (rAF-IL12) against CT26 colon cancer cells.MethodsThe cytotoxicity effect of rAF-IL12 against CT26 colon cancer cell line was determined by MTT assay. Based on the IC50 value from the anti-proliferative assay, further downward assays such as Annexin V FITC and cell cycle progression were carried out and measured by flow cytometry. Then, the in vivo study was conducted where the rAF-IL12 viral injections were given at the intra-tumoral site of the CT26 tumour-burden mice. At the end of the experiment, serum biochemical, T cell immunophenotyping, serum cytokine, histopathology of tumour and organ section, TUNEL assay, and Nanostring gene expression analysis were performed.ResultsThe rAF-IL12 induced apoptosis of CT26 colon cancer cells in vitro as revealed in the Annexin V FITC analysis and also arrested the cancer cells progression at G1 phase of the cell cycle analysis. On the other hand, the rAF-IL12 significantly (p < 0.05) inhibited the growth of CT26 tumour in Balb/c mice and had regulated the immune system by increasing the level of CD4 + , CD8 + , IL-2, IL-12, and IFN-γ. Furthermore, the expression level of apoptosis-related genes (bax and p53) was up-regulated as a result of the rAF-IL12 treatment. Additionally, the rAF-IL12 had also down-regulated the expression level of KRAS, BRAF, MAPK1, Notch1, CCL2, and VEGF oncogenes. Besides, rAF-IL12 intra-tumoral delivery was considered safe and not hazardous to the host as evidenced in pathophysiology of the normal tissues and organs of the mice as well as from the serum biochemistry profile of liver and kidney.ConclusionsThese results indicated that rAF-IL12 had better anti-tumoral and cytotoxicity effects compared to its parental wild-type, AF2240-i in combatting the CT26 colon cancer model.
Highlights
Oncolytic viruses have emerged as an alternative therapeutic modality for cancer as they can replicate in tumour cells and induce toxic effects leading to apoptosis
Najmuddin et al Cancer Cell Int (2020) 20:278 intra-tumoral delivery was considered safe and not hazardous to the host as evidenced in pathophysiology of the normal tissues and organs of the mice as well as from the serum biochemistry profile of liver and kidney. These results indicated that rAF-IL12 had better anti-tumoral and cytotoxicity effects compared to its parental wild-type, AF2240-i in combatting the CT26 colon cancer model
In Vitro Cytotoxicity Effects of rAF‐IL12 in CT26 Cells Cytotoxic effects of rAF-IL12 against CT26 colon cancer cell line in comparison to the parental Newcastle disease virus (NDV), AF2240-i was assessed by 3- [4 (MTT) assay (Fig. 2)
Summary
Oncolytic viruses have emerged as an alternative therapeutic modality for cancer as they can replicate in tumour cells and induce toxic effects leading to apoptosis. Newcastle disease virus (NDV) was once a threat to the poultry producers worldwide It negatively impacts upon egg production, egg weight, and mortality towards avian since its outbreak in 1926s [1, 2]. Despite causing devastating effects on poultry industry, NDV is known for its pronounced anti-tumoral effect and has the potential to be used as a therapeutic agent in the treatment of cancer. It is a replication-competent oncolytic virus which selectively replicates in cancer cells efficiently and destroys them without compromising the normal cells [4]. It has been demonstrated that NDV-LaSota strain expressing the rabies virus glycoprotein enhanced the apoptotic induction of lung adenocarcinoma A549 cells [4]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
