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


CONCLUSIONS
These in vitro findings suggest that a combination of TAC-101 and cisplatin may be a potential new treatment for ovarian clear cell adenocarcinoma.
Ezawa
Sachiko
S
Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Suzuki
Nao
N
Ohie
Shinji
S
Higashiguchi
Atsushi
A
Hosoi
Fumihito
F
Kitazato
Kenji
K
Susumu
Nobuyuki
N
Aoki
Daisuke
D
D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014297:Trimethylsilyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*
D001565:Benzoates; C112689:TAC 101; D014297:Trimethylsilyl Compounds; D002945:Cisplatin