PhD Dissertation at the College of Medicine, University of Babylon on Colorectal Cancer
The Department of Microbiology at the College of Medicine, University of Babylon, discussed the PhD dissertation of student Alaa Kazem Hameed, entitled:
“Immunological Variables of Colorectal Cancer Against Certain Drugs and Their Relation to SARS-CoV-2: An In Vitro Study”,
supervised by Prof. Dr. Ifad Karim Al-Shibli and Prof. Dr. Rana Iyad Ghalib.
The discussion was attended by the Scientific Assistant, Asst. Prof. Dr. Ashraf Mohamed Ali Hussein, along with several faculty members, academics, and postgraduate students.
During her defense, the researcher explained that cancer patients are particularly vulnerable to SARS-CoV-2 infection due to their weakened immune status and the expression of viral entry receptors in tumor tissues.
The interactions between viral infection and cancer biology have raised concerns about potential changes in disease progression, treatment response, and immune regulation in cancer patients with COVID-19. Therefore, understanding how SARS-CoV-2 and anti-COVID-19 drugs interact with cancer cells is essential.
This study aimed to explore the interactions between viral infections and cancer biology, the possible changes in disease progression, treatment response, and immune regulation in cancer patients with COVID-19, and to understand how anti-COVID-19 drugs interact with cancer cells.
Three drugs were tested in different doses and combinations on the SW-480 colorectal cancer cell line:
• The chemotherapy drug Cisplatin,
• The COVID-19 drug Tocilizumab (ACTEMRA®),
• The COVID-19 drug Remdesivir (Veklury®).
Cytotoxicity of Cisplatin, Actemra, and Remdesivir on SW480 cells was evaluated using the MTT assay.
The results showed that Cisplatin treatment caused a statistically significant reduction in cell viability (P ? 0.001) across all tested concentrations compared to the control group.
Remdesivir significantly reduced cell viability, reaching nearly zero at high concentrations, showing a significant effect (P < 0.05), especially in infected cells.
By contrast, Actemra showed minimal cytotoxicity compared to the other drugs.
Immune markers (ACE2, CD147, IL-17, IL-23, TGF-?, and TNF-?) were evaluated in the SW480 cells treated with Cisplatin, Actemra, and Remdesivir.
The results revealed:
• A dose-dependent increase in ACE2, CD147, and IL-17 levels after Cisplatin treatment.
• IL-23 and TGF-? levels remained relatively constant across different doses, indicating that Cisplatin had no significant effect on their expression.
• A gradual decrease in TNF-? expression with increasing Cisplatin concentrations.
Similarly, Actemra showed a dose-dependent effect on ACE2 expression, while IL-17, IL-23, and TGF-? levels plateaued.
Remdesivir had a dose-dependent effect on ACE2 expression:
• Low to moderate doses increased ACE2 expression,
• High doses caused cytotoxic effects and reduced ACE2 levels.
CD147 was not significantly sensitive to low concentrations of Remdesivir.
High doses of Remdesivir showed anti-inflammatory effects, suppressing the production of IL-17, IL-23, and TGF-?, likely through cytotoxic or off-target mechanisms.
Additionally, the notable reduction in TNF-? levels in colorectal cancer cells in response to increasing Remdesivir doses suggests a dose-dependent anti-inflammatory effect of the drug.
The RNA-sequencing (RNA-seq) analysis revealed that 324 genes were commonly expressed across all treatment groups, while each treatment group also showed unique sets of expressed genes