| Abstract | OBJECTIVE: A novel retinoid, TAC-101 (4-[3,5-bis (trimethylsilyl) benzamido] benzoic acid), induces apoptosis of ovarian clear cell adenocarcinoma. The antitumor effect of TAC-101 alone or combined with cisplatin was tested using human ovarian carcinoma. METHODS: Induction of genes related to apoptosis by TAC-101 or cisplatin was assessed by DNA microarray analysis. TAC-101 (8 mg/kg/day orally for 21 days), cisplatin (7 mg/kg intravenously on day 1), or a combination of both drugs at the same dosages was administered to nude mice implanted subcutaneously with RMG-I or RMG-II clear cell adenocarcinoma cells. The antitumor effect was evaluated by calculating the treated/control tumor volume ratio at 21 days after implantation. The histoculture drug response assay was also performed using fresh surgical specimens of human ovarian cancer to determine the 50% inhibitory concentration (IC50). RESULTS: Different apoptosis-related genes were induced by TAC-101 and cisplatin. Compared with control mice, the volume of both RMG-I and RMG-II tumors was significantly reduced (p<0.05) by either drug. The IC50 values of cisplatin and TAC-101 showed a significant correlation (p<0.01). CONCLUSION: These in vitro findings suggest that a combination of TAC-101 and cisplatin may be a potential new treatment for ovarian clear cell adenocarcinoma. |
| Authors | Sachiko Ezawa, Nao Suzuki, Shinji Ohie, Atsushi Higashiguchi, Fumihito Hosoi, Kenji Kitazato, Nobuyuki Susumu, Daisuke Aoki
(Affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.)
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| Journal | Gynecologic oncology
(Gynecol Oncol)
Vol. 108
Issue 3
Pg. 627-31
(Mar 2008)
ISSN: 1095-6859 United States |
| PMID | 18048092
(Publication Type: Journal Article)
|
| Chemical References |
- Benzoates
- TAC 101
- Trimethylsilyl Compounds
- Cisplatin
|
| Topics |
- Adenocarcinoma, Clear Cell
(drug therapy, pathology)
- Animals
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Apoptosis
(drug effects)
- Benzoates
(administration & dosage, pharmacology)
- Cell Line, Tumor
(drug effects)
- Cisplatin
(administration & dosage, pharmacology)
- Female
- Humans
- Inhibitory Concentration 50
- Mice
- Mice, Nude
- Ovarian Neoplasms
(drug therapy, pathology)
- Trimethylsilyl Compounds
(administration & dosage, pharmacology)
|
