OPB-31121, a novel small molecular inhibitor, disrupts the JAK2/STAT3 pathway and exhibits an antitumor activity in gastric cancer cells

We investigated the mechanisms of action and antitumor effects of OPB-31121, a novel STAT3 inhibitor, in gastric cancer cells. OPB-31121 downregulated JAK2 and gp130 expression and inhibited JAK2 phosphorylation which leads to inhibition of STAT3 phosphorylation. OPB-31121 inhibited constitutively activated and IL-6-induced JAK/STAT signaling pathway. OPB-31121 decreased cell proliferation in both gastric cancer cells and in a xenograft model, induced the apoptosis of gastric cancer cells, inhibited the expression of antiapoptotic proteins, and showed synergism with 5-fluorouracil and cisplatin. Taken together, our study suggests that STAT3 inhibition with OPB-31121 can be tested in patients with gastric cancer.

► OPB-31121 is a novel oral STAT3 inhibitor.
► OPB-31121 down-regulates JAK2 and gp130 expression and inhibits JAK2 phosphorylation.
► OPB-31121 inhibits constitutively activated and IL-6-induced JAK/STAT signaling pathway.
► OPB-31121 causes growth inhibition in gastric cancer cells and a xenograft model.
► OPB-31121 shows synergism with 5-fluorouracil and cisplatin.