Disulfiram combined with copper induces immunosuppression via PD-L1 stabilization in hepatocellular carcinoma.

ABSTRACT: As a potential antitumor drug and chemotherapeutic sensitizer, disulfiram combined with Copper (DSF/Cu2+) does not exert considerable antitumor effects on an immunocompetent hepatocellular carcinoma (HCC) model. In this article, we will explore the mechanism underlying the resistance to DSF in HCC. We analyzed the antitumor effect of DSF/Cu2+ in vivo studies. Tumor and immune cells collected from mice were analyzed by flow cytometry. Then, we analyzed the transcriptional changes in liver cancer cells after DSF/Cu2+ treatment by transcriptional expression profiling. The expression of PD-L1 was detected by real-time PCR, Western blotting and flow cytometry. The expression of PARP1 and GSK3β was knocked down by small interfering RNAs (siRNAs). A subcutaneous Hepa1-6 tumor model was used for s

SUBMITTER: Zhou B 

PROVIDER: S-EPMC6895448 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature