OPB-31121, a novel small molecular inhibitor, disrupts the JAK2/STAT3 pathway and exhibits an antitumor activity in gastric cancer cells.
By: Mi-Jung Kim, Hyun-Jin Nam, Hwang-Phill Kim, Sae-Won Han, Seock-Ah Im, Tae-You Kim, Do-Youn Oh, Yung-Jue Bang
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
2013-1-3; doi: 10.1016/j.canlet.2013.02.010
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
2013-1-3; doi: 10.1016/j.canlet.2013.02.010
Abstract
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.
Copyright © 2013. Published by Elsevier Ireland Ltd.
PMID:23402820
