論文 - 詳細
| RRC ID | 18706 |
|---|---|
| 著者 | Tomizawa M, Shinozaki F, Sugiyama T, Yamamoto S, Sueishi M, Yoshida T. |
| タイトル | Insulin-like growth factor-I receptor in proliferation and motility of pancreatic cancer. |
| ジャーナル | World J Gastroenterol |
| Abstract |
AIM:To develop a molecular therapy for pancreatic cancer, the insulin-like growth factor-I (IGF-I) signaling pathway was analyzed. METHODS:Pancreatic cancer cell lines (MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4) were cultured in media with 10 mL/L fetal bovine serum. Western blotting analysis was performed to clarify the expression of IGF-I receptor (IGF-IR). Picropodophyllin (PPP), a specific inhibitor of IGF-IR, LY294002, a specific inhibitor of phosphatidylinositol 3 kinase (PI3K), and PD98059, a specific inhibitor of mitogen-activated protein kinase, were added to the media. After 72 h, a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay was performed to analyze cell proliferation. A wound assay was performed to analyze cell motility with hematoxylin and eosin (HE) staining 48 h after addition of each inhibitor. RESULTS:All cell lines clearly expressed not only IGF-IR but also phosphorylated IGF-IR. PPP significantly suppressed proliferation of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 cells to 36.9% +/- 2.4% (mean +/- SD), 30.9% +/- 5.5%, 23.8% +/- 3.9%, 37.1% +/- 5.3%, 10.4% +/- 4.5%, 52.5% +/- 4.5% and 22.6% +/- 0.4%, at 2 micromol/L, respectively (P < 0.05). LY294002 significantly suppressed proliferation of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 cells to 44.4% +/- 7.6%, 32.9% +/- 8.2%, 53.9% +/- 8.0%, 52.8% +/- 4.0%, 32.3% +/- 4.2%, 51.8% +/- 4.5%, and 30.6% +/- 9.4%, at 50 micromol/L, respectively (P < 0.05). PD98059 did not significantly suppress cell proliferation. PPP at 2 micromol/L suppressed motility of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 cells to 3.0% +/- 0.2%, 0%, 0%, 2.0% +/- 0.1%, 5.0% +/- 0.2%, 3.0% +/- 0.1%, and 5.0% +/- 0.2%, respectively (P < 0.05). LY294002 at 50 micromol/L suppressed motility of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 to 3.0% +/- 0.2%, 0%, 3.0% +/- 0.2%, 0%, 0%, 0% and 3% +/- 0.1%, respectively (P < 0.05). PD980509 at 20 micromol/L did not suppress motility. Cells were observed by microscopy to analyze the morphological changes induced by the inhibitors. Cells in medium treated with 2 micromol/L PPP or 50 micromol/L LY294002 had pyknotic nuclei, whereas those in medium with 20 micromol/L PD98059 did not show apoptosis. CONCLUSION:IGF-IR and PI3K are good candidates for molecular therapy of pancreatic cancer. |
| 巻・号 | 16(15) |
| ページ | 1854-8 |
| 公開日 | 2010-4-21 |
| DOI | 10.3748/wjg.v16.i15.1854 |
| PMID | 20397262 |
| PMC | PMC2856825 |
| MeSH | Animals Apoptosis Cell Line, Tumor Cell Proliferation Chromones / pharmacology Enzyme Inhibitors / pharmacology Gene Expression Regulation, Neoplastic Humans Insulin-Like Growth Factor I / metabolism* Mice Models, Biological Morpholines / pharmacology Pancreatic Neoplasms / metabolism* Pancreatic Neoplasms / pathology* Phosphatidylinositol 3-Kinases / metabolism Podophyllotoxin / analogs & derivatives Podophyllotoxin / pharmacology Receptor, IGF Type 1 / metabolism* Receptor, IGF Type 1 / physiology Signal Transduction Wound Healing |
| IF | 3.665 |
| 引用数 | 31 |
| WOS 分野 | GASTROENTEROLOGY & HEPATOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | PANC-1(RCB2095) NOR-P1(RCB2139) PK-45H(RCB1973) PK-1(RCB1972) PK-59(RCB1901) MIA Paca2(RCB2094) |