論文 - 詳細
| RRC ID | 56006 |
|---|---|
| 著者 | Takashima Y, Horisawa K, Udono M, Ohkawa Y, Suzuki A. |
| タイトル | Prolonged inhibition of hepatocellular carcinoma cell proliferation by combinatorial expression of defined transcription factors. |
| ジャーナル | Cancer Sci |
| Abstract |
Hepatocellular carcinoma (HCC) accounts for a large proportion of liver cancer cases and has an extremely poor prognosis. Therefore, novel innovative therapies for HCC are strongly desired. As gene therapy tools for HCC, 2 hepatic transcription factors (TF), HNF4A and HNF1A, have been used to suppress proliferation and to extinguish cancer-specific characteristics of target cells. However, our present data demonstrated that single transduction of HNF4A or HNF1A had only a limited effect on suppression of HCC cell proliferation. Thus, in this study, we examined whether combinations of TF could show more effective antitumor activity, and found that combinatorial transduction of 3 hepatic TF, HNF4A, HNF1A and FOXA3, suppressed HCC cell proliferation more stably than single transduction of these TF. The combinatorial transduction also suppressed cancer-specific phenotypes, such as anchorage-independent growth in culture and tumorigenicity after transplantation into mice. HCC cell lines transduced with the 3 TF did not recover their proliferative property after withdrawal of anticancer drugs, indicating that combinatorial expression of the 3 TF suppressed the growth of all cell subtypes within the HCC cell lines, including cancer stem-like cells. Transcriptome analyses revealed that the expression levels of a specific gene set involved in cell proliferation were only decreased in HCC cells overexpressing all 3 TF. Moreover, combined transduction of the 3 TF could facilitate hepatic differentiation of HCC cell lines. Our strategy for inducing stable inhibition and functional differentiation of tumor cells using a defined set of TF will become an effective therapeutic strategy for various types of cancers. |
| 巻・号 | 109(11) |
| ページ | 3543-3553 |
| 公開日 | 2018-11-1 |
| DOI | 10.1111/cas.13798 |
| PMID | 30220099 |
| PMC | PMC6215883 |
| MeSH | Animals Carcinoma, Hepatocellular / drug therapy* Carcinoma, Hepatocellular / genetics Cell Differentiation / drug effects Cell Line, Tumor Cell Proliferation / drug effects Gene Expression Regulation, Neoplastic / drug effects Gene Regulatory Networks / drug effects Genetic Vectors / administration & dosage* Genetic Vectors / pharmacology Hep G2 Cells Hepatocyte Nuclear Factor 1-alpha / genetics* Hepatocyte Nuclear Factor 3-gamma / genetics* Hepatocyte Nuclear Factor 4 / genetics* Humans Liver Neoplasms / drug therapy* Liver Neoplasms / genetics Mice Xenograft Model Antitumor Assays |
| IF | 4.751 |
| 引用数 | 10 |
| 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 | 8 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| ヒト・動物細胞 | Hep G2(RCB1886) HuH-7(RCB1942) |