Tabriz Valiasr International Hospital Publication International Journal of Drug Research in Clinics 2980-9835 1 1 2023 02 06 Blockade of CD155 and Interleukin-6 Suppresses Breast Cancer Cell Growth e10 e10 10.34172/ijdrc.2023.e10 EN Atefeh Khodakarami https://orcid.org/0000-0001-6507-5482 Samira Darvishi Hadi Hassannia Mohammad Sadeghi Sana Esmaeeli Vida Hashemi Mohammad Hojjat-Farsangi Farhad Jadidi-Niaragh https://orcid.org/0000-0002-4641-882X Journal Article 10.34172/ijdrc.2023.e10 2023 04 05 2023 05 01 Background: Breast cancer is the foremost common type of cancer worldwide and the leading cause of death related to cancer. Poliovirus receptor (CD155) or nectin-like molecule-5 expression has been shown to increase in tumor cells and bind to the DNAX accessory molecule (DNAM-1)/T cell immunoreceptor with Ig and ITIM domains (TIGIT)/CD69 ligand present on the surface of T and natural killer cells, increasing inflammatory cytokines, including interleukin 6 (IL-6) in the tumor microenvironment. As a result, we intended to simultaneously target both CD155 and IL-6 as an effective therapeutic approach to prevent breast cancer growth. Methods: In this study, 4T1 cells were transfected with small interfering RNA (siRNA) molecules against CD155 and IL-6, using lipofectamine (LP). Target gene expression was analyzed using both the real-time polymerase chain reaction (RT-PCR) and an enzyme-linked immunosorbent assay (ELISA). The methyl thiazolyl tetrazolium (MTT) assay also examined the cytotoxic effect of combined therapy. Results: The results showed that the cells were effectively transfected with LP, resulting in the downregulation of IL-6 and CD155. In addition, the combined silencing of IL-6 and CD155 potently reduced the cellular viability of cancer cells. Conclusion: These findings revealed that the simultaneous targeting of CD155 and IL-6 in breast cancer cells (4T1) is an innovative and efficient therapy strategy to induce apoptosis in malignant cells.