| ID | 106055 |
| Title Alternative | 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
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| Author |
Sato, Momoko
Department of Gastroenterology and Oncology, Institutes of Health Biosciences, University of Tokushima Graduate School
Muguruma, Naoki
University of Tokushima
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Okamoto, Koichi
University of Tokushima
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Yano, Hiromi
University of Tokushima
Sannnomiya, Katsutaka
University of Tokushima
Miyamoto, Hiroshi
University of Tokushima
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Okahisa, Toshiya
University of Tokushima
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Wada, Satoshi
Oe Kyodo Hospital
Iwata, Masao
Eisai Co., Ltd
Takayama, Tetsuji
University of Tokushima
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| Keywords | Apoptosis
ascites
gastric cancer
pladienolide B
RNA splicing
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| Content Type |
Thesis or Dissertation
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| Description | 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.
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| Journal Title |
Cancer Science
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| ISSN | 13497006
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| NCID | AA12100165
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| Publisher | Wiley|Japanese Cancer Association
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| Volume | 105
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| Issue | 1
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| Start Page | 110
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| End Page | 116
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| Published Date | 2013-11-01
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| Remark | 内容要旨・審査要旨・論文本文の公開
内容要旨・審査要旨 : LID201403051005.pdf 論文本文 : LID201405271003.pdf 本論文は, 著者Momoko Satoの学位論文として提出され, 学位審査・授与の対象となっている。 |
| Rights | 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/ )
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| EDB ID | |
| DOI (Published Version) | |
| URL ( Publisher's Version ) | |
| FullText File | |
| language |
eng
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| TextVersion |
ETD
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| MEXT report number | 甲第2660号
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| Diploma Number | 甲医第1186号
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| Granted Date | 2014-01-23
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| Degree Name |
Doctor of Medical Science
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| Grantor |
Tokushima University
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| departments |
Medical Sciences
University Hospital
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