Newcastle disease virus enhances the cytotoxic effects of 5-FU and Alters the expression pattern of microRNAs in human colorectal adenocarcinoma cell line (HT-29 cell line)
Mostafa Eslamimahmoudabadi,1Hadi Esmaeili Gouvarchin Ghaleh,2,*
1. Student Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran 2. Applied Virology Research Center, Baqiyatallah University of medical sciences, Tehran, Iran.
Introduction: Colorectal cancer (CRC) is a prevalent form of malignancy that is often linked to
a poor prognosis, primarily because it is usually diagnosed at an advanced stage. 5-Fluorouracil
(5-FU) is a commonly used chemotherapeutic agent for treating various cancers, sometimes in
combination with other chemotherapies. Virotherapy shows great potential as an effective tool in
combating cancer due to its high level of safety and ability to specifically target cancer cells. The
Newcastle disease virus (NDV) has been found to possess a remarkable safety profile, making it
a promising candidate for medical applications. Notably, this virus exhibits a unique ability to
specifically target tumor cells, which presents an exciting opportunity for its potential use in
combination with chemotherapeutic agents like 5-FU. This study aims to evaluate the
cytotoxic effects of NDV in combination with 5-FU on HT-29 cells, as well as the impact of this
approach on the expression patterns of specific microRNAs.
Methods: In this study, we performed experiments to investigate the hypothesis on the HT-29
human colorectal adenocarcinoma cell line. We employed the non-virulent LaSota strain of NDV
together with 5-FU to assess the cytotoxicity effects and determine the expression levels of miR-
133a-3p, miR-574-3p, and miR-27a-3p in the study groups.
Results: Our study findings indicate that the use of combination therapy, in comparison to
administering 5-FU and NDV alone, can result in more potent cytotoxic effects on colorectal
cancer cells. This therapeutic approach also resulted in a significant upregulation of miR-133a-
3p and miR-574-3p expression, as well as a considerable downregulation of miR-27a-3p
expression in cancer cells.
Conclusion: The remarkable effect of NDV and 5-FU on HT-29 CRC cells in vitro is
impressive. This combinational therapy also regulates cancer cell miRNA expression, improving
therapeutic efficacy. This suggests that this therapeutic approach could be a promising CRC
combination therapy.