JAK2/STAT3 pathway as a therapeutic target in ovarian cancers

Yoshikawa,Tomoyuki; Miyamoto,Morikazu; Aoyama,Tadashi; Soyama,Hiroaki; Goto,Tomoko; Hirata,Junko; Suzuki,Ayako; Nagaoka,Isao; Tsuda,Hitoshi; Furuya,Kenichi; Takano,Masashi

doi:10.3892/ol.2018.8028

JAK2/STAT3 pathway as a therapeutic target in ovarian cancers

Authors:
- Tomoyuki Yoshikawa
- Morikazu Miyamoto
- Tadashi Aoyama
- Hiroaki Soyama
- Tomoko Goto
- Junko Hirata
- Ayako Suzuki
- Isao Nagaoka
- Hitoshi Tsuda
- Kenichi Furuya
- Masashi Takano
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Affiliations: Department of Clinical Oncology, National Defense Medical College Hospital, Tokorozawa, Saitama 359‑8513, Japan, Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Tokorozawa, Saitama 359‑8513, Japan, Department of Host Defense and Biochemical Research, Juntendo University, Graduate School of Medicine, Tokyo 113‑8431, Japan, Department of Basic Pathology, National Defense Medical College Hospital, Tokorozawa, Saitama 359‑8513, Japan
Published online on: February 12, 2018 https://doi.org/10.3892/ol.2018.8028
Pages: 5772-5780

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Abstract

The activation of JAK2/STAT3 pathway has been reported to have critical roles in several solid tumors. The present study aimed to evaluate the correlation between JAK2/STAT3 activation and clinicopathological parameters in ovarian cancer types. Tissue microarrays made from the patients treated at the National Defense Medical College Hospital between 1984 and 2008 were evaluated using immunohistochemical (IHC) stainings. Medical charts of these patients including IHC results were retrospectively analyzed, and prognostic factors for progression‑free survival and overall survival were evaluated. Among 341 enrolled patients, positive expression of p‑STAT3 was observed in 95 cases (28%). Positive p‑STAT3 was an independent worse prognostic factor for overall survival in all the cases. Additionally, p‑STAT3 expression was related with overall survival in patients with clear‑cell histology, but not in serous histology. The effect of an inhibitor of STAT3, niclosamide, was evaluated in ovarian clear‑cell cancer cells, and niclosamide treatment decreased expression of p‑STAT3, leading to increased apoptosis in a dose‑dependent manner in vitro. The activation of JAK2/STAT3 pathway had significant impact on survival of ovarian cancers, especially for the cases with clear‑cell histology. Although further analyses are needed, suppression of this pathway could be a candidate for the treatment of ovarian cancers.

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