Negar Deldadeh
1,2 
, Saeedeh Ghiasvand
3 , Flora Forouzesh
2, Fatemeh Shahriari
4, Hamid Zaferani Arani
5, Mohammad Amin Javidi
1,2* , Mohammad Hadi Niakan
6* 1 Integrative Oncology Department, Breast Cancer Research Center, National Cancer Institute, ACECR, Tehran, Iran
2 Department of Genetics, TeMS.C., Islamic Azad University, Tehran, Iran
3 Department of Biology, Faculty of Science, Malayer University, Malayer, Iran
4 Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
5 Department of Surgery, Shiraz University of Medical Sciences, Shiraz, Iran
6 Trauma Research Center, Shahid Rajaee (Emtiaz) Trauma Hospital, Shiraz University of Medical Sciences, Fars Province, Shiraz, Iran
Abstract
Introduction: According to the efforts made in the field of controlling the coronavirus disease, vaccination was found to be the best choice to cease the spread of the pandemic. Unfortunately, cancer patients, as well as cancer survivors, were categorized as a high-risk priority group for vaccination compared to the normal population before a sufficient assessment of the impact of vaccines on tumor behavior.
Methods: This in vivo investigation attempts to demonstrate the metastasis-inhibitory effect of two famous vaccine brands, Sinopharm and AstraZeneca, in the 4T1 mice model. Single and double doses of each brand were administered to the related group after 10 and 20 days, after the mice's tumor size reached about 250 mm3. As control groups, mice models with the same conditions received one or two doses of ddH2O. After one month, the mice were euthanized by CO2. The mRNA expression level of related genes to metastasis, cell invasion, cell-cell adhesion, the EMT process, and angiogenesis was investigated by real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC). Metastasis to vital organs (heart, lung, kidney, liver, and spleen) was also examined by H&E.
Results: The results revealed a dramatic downregulation of MMP-2/9 and VEGF expression in the vaccinated groups versus the control group. Furthermore, metastasis to vital organs was much less in the vaccinated groups (although some metastatic lesions were seen in the groups that received AstraZeneca, these lesions were much less compared to the control groups).
Conclusion: The main aim of the current study was to assess whether vaccination against COVID-19 exhibits any plausible impact on the metastasis of a TNBC in a mouse model or not. Together, our results hypothesize that the vaccination not only does not have a harmful effect on the tumor, but vaccines may exhibit anti-metastatic effects in preclinical models by reducing pro-cancer markers (such as MMP-2/9 and VEGF) and preventing metastasis to vital organs.