Journal
CANCER LETTERS
Volume 335, Issue 1, Pages 145-152Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2013.02.010
Keywords
OPB-31121; Gastric cancer; STAT3; JAK2; IL-6
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Funding
- Otsuka Pharmaceutical Co., Ltd.
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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. (c) 2013 Elsevier Ireland Ltd. All rights reserved.
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