摘要：The thioredoxin system plays a role in a variety of physiological functions, including cell growth, differenti- ation, apoptosis, tumorigenesis, and immunity. We previously confirmed that butaselen （BS）, a novel thioredoxin reductase inhibitor, can inhibit the growth of various human cancer cell lines, yet the underlying mechanism remains elusive. In this study, we investigated the anti-tumor effect of BS in vivo through regulating the immune system of KM mice. We found that BS inhibits tumor proliferation by promoting the activation of splenic lymphocytes in mice. BS can elevate the percentage of CD^4-CD8^＋ T lymphocytes and the secretion of downstream cytokines in mice via downregulating the expression of programmed death-ligand 1 （PD-L1） on the tumor cells＇ surface in vivo. Further study in HepG2 and BEL-7402 cells showed that decrease of PD-L1 level after BS treatment was achieved by inhibiting signal transducer and activator of transcription 3 （STAT3） phosphorylation. Taken together, our results suggest that BS has a role in promoting the immune response by reducing PD-L1 expression via the STAT3 pathway, and subsequently suppresses tumorigenesis.

摘要：Ethaselen, an organoselenium compound designed and synthesized in the School of Pharmaceutical Sciences, Peking University, has been entitled to independent intellectual property rights both at home and abroad. As one of the novel antitumor drugs, ethaselen has been extensively studied in Phase I clinical trial, and its biological target is thioredoxin reductase. In this review, we focus on the ethaselen＇s efficacy and pharmacological actions, including antitumor effects both in vitro and in vivo, and immunologic functions. These research findings not only provide the theoretical basis for the anticancer study of ethaselen, but also guide the clinical trial of ethaselen.