Silencing Signal Transducer and Activator of Transcription 3 (STAT3) and Use of Anti-Programmed Cell Death-Ligand 1 (PD-L1) Antibody Induces Immune Response and Anti-Tumor Activity.

Abstract

BackgroundThe treatment of cancer is still unable to meet the needs of patients and remains a huge challenge. This study investigated the immune response and anti-cancer effect of silencing STAT3 combined with the use of anti-PD-L1 antibody.Material/MethodsTransfected CT26.WT cells were used to subcutaneously inoculate C57B/L6 mice, which were subsequently injected with anti-PD-L1 antibody. Treated mice were examined for tumor formation and inflammation using HE staining. Tumors were investigated for apoptosis using the TUNEL assay. The expression of STAT3, PD-L1, and C-met was studied immunohistochemistrially and by using PCR and Western blot analysis.ResultsFour weeks after inoculation, tumors were observed in the inoculated mice. HE staining showed obvious inflammation in mice injected with cells that were silenced for STAT3 and injected with PD-L1 antibody. TUNEL assay showed low level of apoptosis in mice injected with cells silenced for STAT3 or injected with PD-L1 antibody, and higher level of apoptosis following combined treatment of STAT3 silencing and PD-L1 antibody injection. Immunohistochemistry, PCR, and Western blot analyses revealed that the expression of C-met, PD-L1, and STAT3 was significantly reduced in tumors following the combined treatment. Compared with treatment of STAT3 silencing or PD-L1 antibody injection, the combined treatment enhanced apoptosis.ConclusionsSilencing STAT3 and PD-L1 antibody injection in combination increased apoptosis in tumor cells and thus offers better anti-cancer activity.