2003 Fiscal Year Final Research Report Summary
Retinoid upregulates the sensitivity of cancer cells to a cytokine by inducing the cytokine receptor
| Project/Area Number |
13557048
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 展開研究 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Gifu University |
|---|
Principal Investigator |
MORIWAKI Hisataka Gifu University School of Medicine, Dept of Gastroenterology and Hepatology, Professor, 医学部, 教授 (50174470)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OKUNO Masataka Gifu University School of Medicine, Associate Professor, 医学部, 助教授 (10204140)
OMORI Masahide Tokai Women's College, President, 学長 (30278212)
SHIDOJI Yoshihiro Nagasaki Siebolt Univ, Dept of Nursery and Nutrition, Professor, 栄養看護学部, 教授 (00111518)
SHIRATORI Yoshimune Gifu University School of Medicine, Research Associate, 医学部附属病院, 助手 (20313877)
|
|---|
| Project Period (FY) |
2001 – 2003
|
| Keywords | Liver cancer / Chemoprevention / Immunoprevention / Interferon / Apoptosis / Retinoid / Interferon receptor / STAT1 |
|---|
| Research Abstract |
Acyclic retinoid, a synthetic retinoid analog, as well as interferons (IFNs)-α and -β induce apoptosis in hepatocellular carcinoma (HCC) cells and are used clinically in the prevention of HCC. Here, we show that acyclic retinoid acts synergistically with IFNs in suppressing the growth and inducing apoptosis (as characterized by DNA fragmentation and chromatin condensation) in 5 human HCC cell lines (JHH7,HuH7,PLC/PRF/5,HLE and HLF). This synergism was only observed when cells were pretreated with the aeyclic retinoid, whereas natural retinoic acids (all-trans and 9-cis retinoic acid) were ineffective. This promotion may be due to up-regulation of type 1 IFN receptor (IFNR) expression by the retinoid. Accordingly, incubation with anti-type 1 IFNR antibody abolished the synergy. Enhanced IFNR expression was accompanied by increased expression and DNA-binding activity of STAT1, an intracellular signal transducing molecule of IFNR, and increased induction of 2',5'-oligoadenyl-5'-triphosphate synthetase, which is a target gene of STAT1. Acyclic retinoid did not have any effects on the growth of normal human hepatocytes (Hc) probably due to lack of IFNR and STAT1 up-regulation. These results provide a rationale for combined biochemoprevention of HCC using acyclic retinoid and IFN-β.
|
