ヨゴサワ　シンゴ   YOGOSAWA Shingo   与五沢　真吾    所属   埼玉医科大学  保健医療学部 臨床検査学科    職種   准教授
論文種別	学術雑誌(原著)
言語種別	英語
査読の有無	査読あり
表題	Three Combined Treatments, a Novel HDAC Inhibitor OBP-801/YM753, 5-Fluorouracil, and Paclitaxel, Induce G(2) Phase Arrest Through the p38 Pathway in Human Ovarian Cancer Cells
掲載誌名	正式名：ONCOLOGY RESEARCH ISSNコード：0965-0407/1555-3906
出版社	COGNIZANT COMMUNICATION CORP
巻・号・頁	25(8),1245-1252頁
著者・共著者	Makoto Akiyama,Yoshihiro Sowa,Tomoyuki Taniguchi,Motoki Watanabe,Shingo Yogosawa,Jo Kitawaki,Toshiyuki Sakai
発行年月	2017
概要	Ovarian cancer is the most lethal disease among gynecological malignancies. More effective therapy is required to counter high recurrence rates and chemotherapy resistance. We investigated the efficacy and molecular mechanisms of three combined treatments (TCTs)-a novel histone deacetylase (HDAC) inhibitor OBP-801/YM753, 5-fluorouracil (5-FU), and paclitaxel (PTX)-in human ovarian cancer SKOV-3 and OVCAR-3 cells. The inhibition of cell growth was stronger with TCTs than with each single agent and with two combined treatments. The TCTs significantly induce G(2) phase arrest in both cell lines. We then analyzed the molecular mechanisms and found that the TCTs increased the phosphorylation of p38 (Thr180/Tyr182), decreased the expression of CDC25C, and increased the phosphorylation of CDC2 (Tyr15), an inactive form of CDC2. To examine the responsibilities of the p38 pathway for G(2) phase arrest induced by the TCTs, we employed the p38 inhibitor SB203580. SB203580 inhibited G(2) phase arrest, suppression of CDC25C, and phosphorylation of CDC2 (Tyr15) induced by the TCTs. These results suggest that the TCTs can induce G(2) phase arrest through activation of the p38 signaling pathway. We therefore believe that this combination is promising as a novel therapeutic strategy against ovarian cancer.
DOI	10.3727/096504017X14850164661097
PMID	28117030