論文 - 詳細
| RRC ID | 44971 |
|---|---|
| 著者 | Sato M, Muguruma N, Nakagawa T, Okamoto K, Kimura T, Kitamura S, Yano H, Sannomiya K, Goji T, Miyamoto H, Okahisa T, Mikasa H, Wada S, Iwata M, Takayama T. |
| タイトル | High antitumor activity of pladienolide B and its derivative in gastric cancer. |
| ジャーナル | Cancer Sci |
| Abstract |
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. |
| 巻・号 | 105(1) |
| ページ | 110-6 |
| 公開日 | 2014-1-1 |
| DOI | 10.1111/cas.12317 |
| PMID | 24635824 |
| PMC | PMC4317874 |
| MeSH | Aged Aged, 80 and over Animals Antineoplastic Agents / therapeutic use* Apoptosis / drug effects Apoptosis / genetics Cell Line, Tumor Cyclin E / genetics Cyclin-Dependent Kinase Inhibitor p16 / genetics Epoxy Compounds / therapeutic use* Female Humans Macrolides / therapeutic use* Male Mice Mice, SCID Middle Aged RNA Splicing / drug effects RNA Splicing / genetics Random Allocation Stomach Neoplasms / drug therapy* Stomach Neoplasms / genetics Xenograft Model Antitumor Assays |
| IF | 4.966 |
| 引用数 | 23 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HGC-27(RCB0500) NUGC-4(RCB1939) Lu99(RCB1900) T3M-11(RCB1022) MDA-MB-453(RCB1192) |