2026-03-09T09:44:51Z https://tokushima-u.repo.nii.ac.jp/oai

oai:tokushima-u.repo.nii.ac.jp:02006113 2025-04-28T07:16:33Z 1713853213384:1713853296295:1716267876683:1716268551628

Cytotoxic effects of 15-deoxy-Δ12,14-prostaglandin J2 alone and in combination with dasatinib against uterine sarcoma in vitro 15-deoxy-Δ12,14-prostaglandin J2の単剤とダサチニブの併用療法は子宮肉腫の増殖を抑制する CYTOTOXIC EFFECT OF 15d-PGJ2 AGAINST UTERINE SALCOMA 00724121 河北, 貴子 カワキタ, タカコ Kawakita, Takako 河北 カワキタ Kawakita 貴子 タカコ Takako 70380037 西村, 正人 ニシムラ, マサト Nishimura, Masato 西村 ニシムラ Nishimura 正人 マサト Masato 炬口, 恵理 タキグチ, エリ Takiguchi, Eri 30748588 阿部, 彰子 アベ, アキコ Abe, Akiko 阿部 アベ Abe 彰子 アキコ Akiko 20160070 苛原, 稔 イラハラ, ミノル Irahara, Minoru 苛原 イラハラ Irahara 稔 ミノル Minoru open access © Kawakita et al. This is an open access article distributed under the terms of Creative Commons Attribution License. 15‑deoxy‑Δ12,14‑prostaglandin J2 uterine sarcoma dasatinib MAPK ERK AKT Effective chemotherapeutic strategies for uterine sarcoma are lacking; existing therapies achieve poor response rates. Previous studies have identified the prostaglandin 15-deoxy- Δ12,14-prostaglandin J2 (15d-PGJ2) as a potential anticancer treatment; however, its effectiveness in uterine sarcoma has not been examined. Furthermore, the molecular mechanisms underlying the cytotoxic mechanism of 15d-PGJ2 remain unclear. Here, we evaluated the effects of 15d-PGJ2 alone and in combination with the tyrosine kinas inhibitor (TKI) dasatinib in uterine sarcoma cell lines (MES-SA, MES-SA/DX5 and SKN). 15d-PGJ2 inhibited cell growth and increased apoptosis. Western blotting demonstrated that 15d-PGJ2 treatment increased MEK and ERK phosphorylation, and decreased levels of phosphorylated AKT. Dasatinib in combination with 15d-PGJ2 significantly reduced cell proliferation compared with 15d-PGJ2 alone, and repressed both the AKT and MAPK pathways. The cell growth inhibition rate in the PGJ2 was 21.5±12.0, 35.3±5.4 and 28.3±4.2%, respectively (MES-SA, MES-SA/DX5 and SKN cell lines) and the cell growth inhibition rate in the combination therapy was significantly higher compared with 15d-PGJ2 alone (MES-SA; 64.2±0.8, MES-SA/DX5;23.9±8.2 and SKN; 41.4±17.6%). The PGJ2 IC50 determined by MTT assay was 27.41,10.46 and 17.38 μmol/l, respectively (MES-SA, MES-SA/DX5 and SKN cell lines) and the dasatinib IC50 was 6.68,17.30 and 6.25 μmol/l, respectively. Our findings demonstrate that 15d-PGJ2 suppresses proliferation by inactivating the AKT pathway in uterine sarcoma. Furthermore, combining 15d-PGJ2 with dasatinib produced a synergistic effect on cancer cell inhibition by repressing 15d-PGJ2-mediated activation of MAPK signaling, and further repressing AKT signaling. These results suggest that 15d-PGJ2 could be used in combination with dasatinib as a potential therapeutic approach for uterine sarcoma. Spandidos publications 2017-04-18 eng doctoral thesis NA 339206 https://tokushima-u.repo.nii.ac.jp/records/2006113 https://doi.org/10.3892/etm.2017.4346 10.3892/etm.2017.4346 17920981 17921015 AA12610820 Experimental and Therapeutic Medicine 13 6 2939 2945 甲医第1325号 博士（医学） 2017-03-06 徳島大学 https://tokushima-u.repo.nii.ac.jp/record/2006113/files/LID201705191007.pdf application/pdf 337 KB 2017-05-20 https://tokushima-u.repo.nii.ac.jp/record/2006113/files/LID201706261001.pdf application/pdf 2.36 MB 2017-06-27