Growth-inhibitory effects of the synthetic retinoid CD437 against ovarian carcinoma models in vitro and in vivo.
The activity of CD437¿6-[3-(1-adamantyl)-4 hydroxyphenyl]-2-naphthalene carboxylic acid¿, a relatively selective activator of RAR-gamma, was evaluated against four human ovarian-carcinoma cell lines : PE01, PE04 (a Pt-resistant in vivo-derived counterpart of PE01), PE01CDDP (a Pt-resistant in vitro-derived model of PE01) and PE014. Growth inhibition was observed after 3 and 6 days of exposure to sub-micromolar concentrations as assessed by a reduction in cell number. IC50 values against PE01, PE04, PE01CDDP and PE014 were 0.09, 0.21, 0.12 and 0.28 microM (day 3) and 0.1, 0.14, 0.07 and 0.17 microM (day 6), respectively. Cisplatin-resistant cell lines were as responsive as cisplatin-sensitive lines, indicating potential activity in resistant disease. CD437 was also evaluated against the PE04 xenograft grown in nude mice using daily doses of 20 (days 0-4) and 10 mg/kg (days 0-4 and 7-11) given either by i.p. delivery or oral administration. Significant growth inhibition (P < 0.05) was obtained for both doses and by both routes. These data provide further support for the view that retinoids have value for the treatment of ovarian cancer.
ICRF Medical Oncology Unit, Western General Hospital, Edinburgh, UK.
S P
SP
Langdon
G J
GJ
Rabiasz
A A
AA
Ritchie
U
U
Reichert
P
P
Buchan
W R
WR
Miller
J F
JF
Smyth
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012176:Retinoids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C099555:CD 437; D012176:Retinoids; D002945:Cisplatin