Inflammatory Bowel Diseases

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Inflammatory Bowel Diseases:
doi: 10.1097/MIB.0b013e318293c5e0
Original Basic Science Articles

Oroxylin A Inhibits Colitis-associated Carcinogenesis Through Modulating the IL-6/STAT3 Signaling Pathway

Yang, Xi MS*; Zhang, Fengyi MS; Wang, Yajing PhD*; Cai, Min MS*; Wang, Qing MD; Guo, Qinglong PhD*; Li, Zhiyu PhD§; Hu, Rong PhD*

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Background: Patients with inflammatory bowel disease, which includes ulcerative colitis and Crohn’s disease, are at a significantly increased risk of developing colorectal cancer, and aberrant interleukin (IL)-6/STAT3 signaling pathway exists in both inflammatory bowel disease and inflammation-related gastrointestinal cancers. We have previously found that oroxylin A inhibited the NF-κB signaling in human colon tumor HCT-116 cells. However, whether oroxylin A could inhibit the colitis-associated carcinogenesis remains to be determined.

Methods: HCT-116 cells were treated with various concentrations of oroxylin A. Expression of relative proteins of IL-6/STAT3 signaling pathway was assayed by Western blot and immunofluorescence analysis. Mouse model for colitis-associated colorectal cancer was induced by a combined treatment with 10 mg/kg azoxymethane (AOM) followed by 3 cycles of 2.5% dextran sodium sulfate in C57BL/6 mice. IL-6 and IL-1β gene expression were analyzed by quantitative real-time PCR. Expression of relative proteins was examined by immunohistochemistry and Western blot.

Results: Oroxylin A effectively inhibited IL-6/STAT3 pathway in human HCT-116 cells, and the effect of oroxylin A was reversible. Dietary administration of oroxylin A throughout the experimental period significantly reduced the tumor burden, inhibited cell proliferation, and induced apoptosis in colon carcinomas. The expression of inflammatory cytokines IL-6 and IL-1β decreased in tumors in oroxylin A–treated mice. The IL-6/STAT3 signaling pathway was attenuated in oroxylin A–treated mice.

Conclusions: Our results demonstrated that oroxylin A inhibits colitis-associated carcinogenesis through modulating IL-6/STAT3 pathway in AOM/dextran sodium sulfate mouse model and in HCT-116 cells.

© Crohn's & Colitis Foundation of America, Inc.

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