論文 - 詳細
| RRC ID | 47420 |
|---|---|
| 著者 | Hoang NT, Kadonosono T, Kuchimaru T, Kizaka-Kondoh S. |
| タイトル | Hypoxia-inducible factor-targeting prodrug TOP3 combined with gemcitabine or TS-1 improves pancreatic cancer survival in an orthotopic model. |
| ジャーナル | Cancer Sci |
| Abstract |
Pancreatic cancer is one of the most lethal digestive system cancers with a 5-year survival rate of 4-7%. Despite extensive efforts, recent chemotherapeutic regimens have provided only limited benefits to pancreatic cancer patients. Gemcitabine and TS-1, the current standard-of-care chemotherapeutic drugs for treatment of this severe cancer, have a low response rate. Hypoxia is one of the factors contributing to treatment resistance. Specifically, overexpression of hypoxia-inducible factor, a master transcriptional regulator of cell adaption to hypoxia, is strongly correlated with poor prognosis in many human cancers. TAT-ODD-procaspase-3 (TOP3) is a protein prodrug that is specifically processed and activated in hypoxia-inducible factor-active cells in cancers, leading to cell death. Here, we report combination therapies in which TOP3 was combined with gemcitabine or TS-1. As monotherapy, gemcitabine and TS-1 showed a limited effect on hypoxic and starved pancreatic cancer cells, whereas co-treatment with TOP3 successfully overcame this limitation in vitro. Furthermore, combination therapies of TOP3 with these drugs resulted in a significant improvement in survival of orthotopic pancreatic cancer models involving the human pancreatic cancer cell line SUIT-2. Overall, our study indicates that the combination of TOP3 with current chemotherapeutic drugs can significantly improve treatment outcome, offering a promising new therapeutic option for patients with pancreatic cancer. |
| 巻・号 | 107(8) |
| ページ | 1151-8 |
| 公開日 | 2016-8-1 |
| DOI | 10.1111/cas.12982 |
| PMID | 27270607 |
| PMC | PMC4982586 |
| MeSH | Animals Cell Line, Tumor Deoxycytidine / administration & dosage Deoxycytidine / analogs & derivatives* Deoxycytidine / pharmacology Fluorouracil / pharmacology Gemcitabine Humans Hypoxia-Inducible Factor 1 / antagonists & inhibitors* Male Mice Mice, Inbred BALB C Pancreatic Neoplasms / metabolism* Pancreatic Neoplasms / pathology* Prodrugs / metabolism* Prodrugs / pharmacology Recombinant Fusion Proteins / metabolism* Recombinant Fusion Proteins / pharmacology Silicates / administration & dosage Silicates / pharmacology* Survival Analysis Titanium / administration & dosage Titanium / pharmacology* Tumor Hypoxia Xenograft Model Antitumor Assays* |
| IF | 4.966 |
| 引用数 | 9 |
| 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
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 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 | |
| 遺伝子材料 | pGEX-6P-3/GST-TAT-ODD/3-0-Casp3 (RDB14403) pEF/HRE-Fluc (RDB14404). |