論文 - 詳細
| RRC ID | 18120 |
|---|---|
| 著者 | Yasui T, Ohuchida K, Zhao M, Cui L, Onimaru M, Egami T, Fujita H, Ohtsuka T, Mizumoto K, Matsumoto K, Tanaka M. |
| タイトル | Adenoviral therapy is more effective in gemcitabine-resistant pancreatic cancer than in gemcitabine-sensitive cells. |
| ジャーナル | Anticancer Res |
| Abstract |
BACKGROUND:Although gemcitabine is the standard treatment for pancreatic cancer, this particular type of cancer develops rapidly and has intrinsic chemoresistance. Chemoresistance plays a critical role in tumor progression, invasion and migration. Nevertheless, the effect of adenoviral therapy on chemoresistant cancer cells has not been studied. In this study, we compared the efficacy of adenoviral therapy in parental and chemoresistant pancreatic cancer cells. MATERIALS AND METHODS:To establish gemcitabine-resistant cells, pancreatic cancer SUIT2 cells were exposed to increasing concentrations of gemcitabine. Both parental and chemoresistant cells were infected with adenoviruses expressing either green fluorescent protein (Ad-GFP) or the hepatocyte growth factor antagonist, NK4 (Ad-NK4). To investigate the transduction efficacy, GFP expression and NK4 concentrations were measured and an invasion assay was used to investigate the efficacy of the adenoviral therapy. RESULTS:The 50% inhibitory concentration of gemcitabine was <10 nM in the parental SUIT-2 cells, while it was >1 μM in gemcitabine-resistant cells. A large number of gemcitabine-resistant cells were GFP-positive compared with only a small number of parental cells (p<0.05). The NK4 expression level was significantly higher in gemcitabine-resistant cells than in parental cells (p<0.05). The supernatant from Ad-NK4-infected gemcitabine-resistant cells significantly inhibited the invasion of cancer cells compared with that from Ad-NK4-infected parental cells (p<0.05). CONCLUSION:Both the efficiency of transduction and the therapeutic efficacy of adenoviral therapy were higher in gemcitabine-resistant cells than in parental cells, suggesting that adenoviral gene therapy is more effective in patients with gemcitabine-resistant pancreatic cancer. |
| 巻・号 | 31(4) |
| ページ | 1279-87 |
| 公開日 | 2011-4-1 |
| PII | 31/4/1279 |
| PMID | 21508376 |
| MeSH | Adenoviridae / genetics* Antimetabolites, Antineoplastic / therapeutic use Biomarkers, Tumor / genetics Blotting, Western Cell Adhesion Cell Line, Tumor Cell Movement Cell Proliferation Deoxycytidine / analogs & derivatives* Deoxycytidine / therapeutic use Drug Resistance, Neoplasm / genetics* Genetic Therapy* Green Fluorescent Proteins / genetics Hepatocyte Growth Factor / genetics* Humans Pancreatic Neoplasms / genetics* Pancreatic Neoplasms / therapy* RNA, Messenger / genetics Reverse Transcriptase Polymerase Chain Reaction Transgenes / physiology |
| IF | 1.994 |
| 引用数 | 4 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | MRC-5 (RCB0211) MRC-5 known PDL (RCB0218) |