CD155 Downregulation Synergizes With Doxorubicin To Induce Breast Cancer Cell Apoptosis

Objective: CD155,also called poliovirus receptor(PVR)or nectin-like 5(Necl-5),is involved in cell proliferation,apoptosis and motility.CD155 has been shown to be overexpressed in cancer tissues,and play an anti-apoptotic role.Moreover,chemotherapy drugs have been observed to upregulate CD155 expression in tumor cells.In this study,we intend to determine the effect of Adriamycin(Adr)on CD155 expression in breast cancer cells,and evaluate the effect of CD155 downregulation on Adr-induced breast cancer cell apoptosis.Methods: CD155 expression in breast cancer cells was detected by immunobloting analysis,immunofluorescence staining and real-time PCR analysis.CD155 shRNA lentiviruses were used to transfect 4T1 cells to downregulate CD155 expression.Breast cancer cell apoptosis was evaluated by flow cytometry in vtro.4T1 cells were injected into the fat pad of BALB/C mouse to establish breast cancer xenograft model.CD155 expression in mouse breast cancer tissues was detected by immunohistochemistry.Breast cell apoptosis was examined by TUNEL staining in vivo.Results: In vitro study showed that Adr upregulated CD155 expression in human breast cancer cell MCF-7,T-47 D and MDA-MB-231,and mouse breast cancer cell 4T1;CD155 shRNA transfection downregulated CD155 expression and blocked Adr-induced CD155 upregulation;CD155 downregulation synergized with Adr to induce apoptosis,although they could induce apoptosis alone.In vivo study showed that Adr upregulated CD155 expression in mouse breast cancer tissues;CD155 shRNA transfection downregulated CD155 expression and blocked Adr-induced CD155 upregulation;CD155 downregulation synergized with Adr to induce apoptosis and inhibit growth,although they could induce apoptosis and inhibit growth alone.Conclusion: Adr induces CD155 expression in breast cancer cells,and CD155 downregulation synergizes with Adr to promote cancer cell apoptosis,suggesting breast cancer cell may exhibit resistant to Adr through CD155 upregulation.