論文 - 詳細
| RRC ID | 42341 |
|---|---|
| 著者 | Sako T, Nakayama Y, Minagawa N, Inoue Y, Onitsuka K, Katsuki T, Tsurudome Y, Shibao K, Hirata K, Nagata N, Ohie S, Kohno K, Itoh H. |
| タイトル | 4-[3,5-Bis(trimethylsilyl)benzamido] benzoic acid (TAC-101) induces apoptosis in colon cancer partially through the induction of Fas expression. |
| ジャーナル | In Vivo |
| Abstract |
BACKGROUND:4-[3,5-Bis (trimethylsilyl) benzamido] benzoic acid (TAC-101) is a novel retinobenzoic acid derivative, which has a specific binding affinity to the retinoic acid receptors (RAR)-alpha and -beta. Apoptotic induction by TAC-101 was investigated using a rat hepatic metastatic model of rat RCN-9 colon cancer cells in vivo and FACScan analysis with the DLD-1 human colon cancer cell line in vitro. MATERIALS AND METHODS:Hepatic metastatic tumors were induced using intra-portal injection of RCN-9 cells into F344 rats in vivo. TAC-101 (8 mg/kg) was orally administered for 5 consecutive days a week for 4 weeks. Subsequently, hepatic tumors were counted after laparotomy. Apoptotic index (A.I.) in the hepatic tumors was evaluated using immunohistochemistry for single-stranded DNA. The proliferative index (P.I.), Fas and Fas ligand were also immunohistochemically evaluated. Moreover, evaluation of apoptosis by TAC-101 in vitro using FACScan analysis was performed in the DLD-1 human colon cancer cell line. RESULTS:Oral administration of TAC-101 resulted in a significant inhibition of hepatic metastasis without weight loss of the rats. TAC-101 significantly decreased P. I. but increased A. I. in the hepatic metastatic tumors. TAC-101 did not affect the expression of Fas ligand, but obviously increased the expression of Fas in the metastatic tumors. Moreover, TAC-101 induced early apoptosis in DLD-1 cells in a time-dependent manner in vitro. CONCLUSION:These findings suggest that TAC-101 inhibits hepatic metastasis of colon cancer and induces apoptosis partially through enhanced Fas expression. |
| 巻・号 | 19(1) |
| ページ | 125-32 |
| 公開日 | 2005-1-1 |
| PMID | 15796164 |
| MeSH | Adenocarcinoma / metabolism* Adenocarcinoma / pathology Administration, Oral Animals Apoptosis / drug effects* Benzoates / administration & dosage Benzoates / pharmacology* Cell Line, Tumor Colonic Neoplasms / metabolism* Colonic Neoplasms / pathology Disease Models, Animal Dose-Response Relationship, Drug Humans Immunohistochemistry Liver Neoplasms / chemically induced Liver Neoplasms / secondary Male Neoplasm Metastasis / prevention & control Rats Rats, Inbred F344 Time Factors Trimethylsilyl Compounds / administration & dosage Trimethylsilyl Compounds / pharmacology* fas Receptor / drug effects fas Receptor / metabolism* |
| IF | 1.541 |
| 引用数 | 6 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL |
| リソース情報 | |
| ヒト・動物細胞 | RCN-9(RCB0511) |