論文 - 詳細
| RRC ID | 61976 |
|---|---|
| 著者 | Weber H, Leal P, Stein S, Kunkel H, García P, Bizama C, Espinoza JA, Riquelme I, Nervi B, Araya JC, Grez M, Roa JC. |
| タイトル | Rapamycin and WYE-354 suppress human gallbladder cancer xenografts in mice. |
| ジャーナル | Oncotarget |
| Abstract |
Gallbladder cancer (GBC) is a highly malignant tumor characterized by a poor response to chemotherapy and radiotherapy. We evaluated the in vitro and in vivo antitumor efficacy of mTOR inhibitors, rapamycin and WYE-354. In vitro assays showed WYE-354 significantly reduced cell viability, migration and invasion and phospho-P70S6K expression in GBC cells. Mice harboring subcutaneous gallbladder tumors, treated with WYE-354 or rapamycin, exhibited a significant reduction in tumor mass. A short-term treatment with a higher dose of WYE-354 decreased the tumor size by 68.6% and 52.4%, in mice harboring G-415 or TGBC-2TKB tumors, respectively, compared to the control group. By contrast, treatment with a prolonged-low-dose regime of rapamycin almost abrogated tumor growth, exhibiting 92.7% and 97.1% reduction in tumor size, respectively, compared to control mice. These results were accompanied by a greater decrease in the phosphorylation status of P70S6K and a lower cell proliferation Ki67 index, compared to WYE-354 treated mice, suggesting a more effective mTOR pathway inhibition. These findings provide a proof of concept for the use of rapamycin or WYE-354 as potentially good candidates to be studied in clinical trials in GBC patients. |
| 巻・号 | 6(31) |
| ページ | 31877-88 |
| 公開日 | 2015-10-13 |
| DOI | 10.18632/oncotarget.5047 |
| PII | 5047 |
| PMID | 26397134 |
| PMC | PMC4741647 |
| MeSH | Animals Antibiotics, Antineoplastic / pharmacology* Apoptosis / drug effects Blotting, Western Cell Movement / drug effects Cell Proliferation / drug effects Drug Therapy, Combination Gallbladder Neoplasms / drug therapy* Gallbladder Neoplasms / pathology Guanine / analogs & derivatives* Guanine / pharmacology Humans Immunoenzyme Techniques Mice Mice, Inbred NOD Mice, SCID Phosphorylation / drug effects Signal Transduction / drug effects Sirolimus / pharmacology* Tumor Cells, Cultured Xenograft Model Antitumor Assays |
| IF | 5.168 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | TGBC2TKB(RCB1130) G-415(RCB2640) |