The BET bromodomain inhibitor i-BET151 impairs ovarian cancer metastasis and improves antitumor immunity.

Ovarian cancer (OC) is a common malignant tumor with a high probability of metastasis. Thus, it is urgently necessary to develop new drugs that inhibit tumor metastasis. Bromodomain and extraterminal (BET) inhibitors targeting bromodomain-containing proteins are currently recognized as novel anticancer agents. Herein, we explored the effects of i-BET151, a BET bromodomain inhibitor, on OC metastasis and on antitumor immunity. Our experiments showed that i-BET151 decreased the viability and induced apoptosis, senescence, and cell cycle arrest of cancer cells. In addition, phosphorylated-Stat3 (Tyr705) amounts OC cell invasion and migration, and expression of matrix metalloproteinases (MMP-9 and MMP-2) decreased. Moreover, tumor metastasis in the abdomen of the OC model was inhibited by i-BET151. Notably, i-BET151-promoted immunogenic cell death (ICD) was confirmed in vivo; it was demonstrated with ICD markers. Furthermore, treatment with i-BET151 promoted infiltration by CD8+ T cells as well as the death of immunogenic tumor cells. In summary, tumor metastasis may be suppressed by i-BET151 via the Stat3 pathway; this approach could be used as a strategy for the treatment of OC.