Effect of all-trans retinoic acid and sodium butyrate in vitro and in vivo on thyroid carcinoma xenografts.
Histone deacetylase (HDAC) inhibitors have been shown to reverse repression of some genes, including retinoic acid (RA) receptor beta2. In this work, we studied the effects of RA alone or combined with the HDAC inhibitor sodium butyrate (NaB) in a poorly differentiated thyroid carcinoma cell line (FTC-133) cultured in vitro or transplanted into nude mice. In vitro, the action of the xenobiotics on cell differentiation was evaluated by the measurement of alkaline phosphatase (ALP) activity. In vivo, FTC cells were injected in nude mice divided into four groups: controls, RA (1 mg/kg), NaB (50 mg/kg) in two daily injections or both RA plus NaB. Body weight, tumoral volume (TV), doubling time of the tumor, specific growth delay and inhibition of tumoral growth at day 35 were determined in each group. In vitro, RA increased the NaB-induced increase in ALP activity. In vivo, body weight and TV decreased with RA or NaB. Specific growth delay significantly increased with RA (72.5%; P < 0.001) and with NaB (31.3%; 0.02 <P <0.01). Inhibition of tumoral growth significantly fell to 50.3% (0.02 < P < 0.01) and 42.9% (0.05 < P < 0.02) with RA and NaB, respectively. The combination of RA with NaB induced no significant change in the different parameters observed in mice treated with RA alone. In conclusion, a synergistic effect between RA and NaB was observed in vitro on cell differentiation. The addition of NaB to RA induces no change in growth inhibition observed with RA alone in nude xenografts.
Massart
Catherine
C
Laboratoire de Génétique Moléculaire et d'Hormonologie, CHU de Pontchaillou, Rennes, France. catherine.massart@chu-rennes.fr
Denais
Annick
A
Gibassier
Jaqueline
J
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D014212:Tretinoin / Q000494:pharmacology*
D002087:Butyrates; D014212:Tretinoin; D000469:Alkaline Phosphatase