A synthetic retinoid, TAC-101 (4-[3,5-bis (trimethylsilyl) benzamido] benzoic acid), plus cisplatin: Potential new therapy for ovarian clear cell adenocarcinoma

Sachiko Ezawa, Nao Suzuki, Shinji Ohie, Atsushi Higashiguchi, Fumihito Hosoi, Kenji Kitazato, Nobuyuki Susumu, Daisuke Aoki

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)627-631
Number of pages5
JournalGynecologic Oncology
Volume108
Issue number3
DOIs
Publication statusPublished - 2008 Mar

Keywords

  • Cisplatin
  • Clear cell adenocarcinoma
  • Histoculture drug response assay
  • Ovarian carcinoma
  • TAC-101

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynaecology

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