High antitumor activity of pladienolide B and its derivative in gastric cancer

• Material Type: 博士論文
• Title: High antitumor activity of pladienolide B and its derivative in gastric cancer
• Author/Editor: Sato, Momoko; Muguruma, Naoki; Nakagawa, Tadahiko; Okamoto, Koichi; Kimura, Tetsuo; Kitamura, Shinji; Yano, Hiromi; Sannnomiya, Katsutaka; Goji, Takahiro; Miyamoto, Hiroshi; Okahisa, Toshiya; Mikasa, Hiroaki; Wada, Satoshi; Iwata, Masao; Takayama, Tetsuji
• Author Heading: Sato, Momoko; Muguruma, Naoki; Nakagawa, Tadahiko; Okamoto, Koichi; Kimura, Tetsuo; Kitamura, Shinji; Yano, Hiromi; Sannnomiya, Katsutaka; Goji, Takahiro; Miyamoto, Hiroshi; Okahisa, Toshiya; Mikasa, Hiroaki; Wada, Satoshi; Iwata, Masao; Takayama, Tetsuji
• Publication, Distribution, etc.: Wiley|Japanese Cancer Association
• Publication Date: 2013-11-01
• Publication Date (W3CDTF): 2013-11-01
• Alternative Title: プラジェノライドＢ及びその誘導体は胃癌に対して高い抗腫瘍活性を有する; Pladienolide is active on gastric cancer
• Periodical title: Cancer Science
• No. or year of volume/issue: 105 1
• Volume: 105
• Issue: 1
• Pages: 110-116
• ISSN (Periodical Title): ISSN : 1349-7006
• Degree grantor/type: 徳島大学
• Date Granted: 2014-01-23
• Dissertation Number: 甲第2660号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Apoptosis; ascites; gastric cancer; pladienolide B; RNA splicing
• Target Audience: 一般
• Note (General): The antitumor activity of pladienolide B, a novel splicing inhibitor, against gastric cancer is totally unknown and no predictive biomarker of pladienolide B efficacy has been reported. We investigated the antitumor activity of pladienolide B and its derivative on gastric cancer cell lines and primary cultured cancer cells from carcinomatous ascites of gastric cancer patients. The effect of pladienolide B and its derivative on six gastric cancer cell lines was investigated using a MTT assay and the mean IC50 values determined to be 1.6 ± 1.2 (range, 0.6–4.0) and 1.2 ± 1.1 (range, 0.4–3.4) nM, respectively, suggesting strong antitumor activity against gastric cancer. The mean IC50 value of pladienolide B derivative against primary cultured cells from 12 gastric cancer patients was 4.9 ± 4.7 nM, indicative of high antitumor activity. When 18 SCID mice xenografted with primary cultured cells from three patients were administered the pladienolide B derivative intraperitoneally, all tumors completely disappeared within 2 weeks after treatment. Histological examination revealed a pathological complete response for all tumors. In the xenograft tumors after treatment with pladienolide B derivative, immature mRNA were detected and apoptotic cells were observed. When the expressions of cell-cycle proteins p16 and cyclin E in biopsied gastric cancer specimens were examined using immunohisctochemistry, positivities for p16 and cyclin E were significantly and marginally higher, respectively, in the low-IC50 group compared with the high-IC50 group, suggesting the possibility that they might be useful as predictive biomarkers for pladienolide B. In conclusion, pladienolide B was very active against gastric cancer via a mechanism involving splicing impairment and apoptosis induction.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.( https://creativecommons.org/licenses/by-nc/3.0/ )
• Related Material (DOI): 10.1111/cas.12317
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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