The independent and combined effects of RAR-, RXR-, and VDR-selective ligands on the growth of squamous cell carcinoma in vitro.
OBJECTIVE
The purpose of our study was to analyze the independent and combined effects of RAR-, RXR-, and VDR-selective ligands on the growth of squamous cell carcinoma to develop new, more effective, and less toxic chemopreventive therapy.


METHODS
The effects of 13-cis retinoic acid (13-cis RA), LG1069 (a highly selective RXR ligand), and vitamin D3 (D3) were analyzed in vitro in the SCC-25 human squamous cell carcinoma cell line. SCC-25 cells were grown in culture medium containing vehicle or hormone at the indicated concentrations. Growth of surviving cells was then assessed using a hemocytometer. The presence of functional vitamin D3 receptor (VDR) was confirmed using gene-transfer experiments with a promoter-lac Z reporter plasmid.


RESULTS
D3 and 13-cis RA have equipotent antiproliferative effects on SCC-25 cells. Furthermore, equimolar LG1069 completely blocks the growth-suppressive effects of D3 but has no effect on the action of 13-cis RA.


CONCLUSIONS
D3 and its analogs, administered alone or in combination with 13-cis RA, may provide more effective and less toxic chemopreventive therapy for the prevention of second primary carcinomas of the head and neck.
Enepekides
D J
DJ
Department of Otolaryngology-Head and Neck Surgery, McGill University, Montreal, Quebec.
Black
M J
MJ
White
J H
JH
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002455:Cell Division / Q000502:physiology; D002762:Cholecalciferol / Q000494:pharmacology* / Q000627:therapeutic use*; D004268:DNA-Binding Proteins / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004359:Drug Therapy, Combination; D006801:Humans; D018167:Receptors, Calcitriol / Q000187:drug effects*; D018168:Receptors, Retinoic Acid / Q000187:drug effects*; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000187:drug effects*; D014212:Tretinoin / Q000494:pharmacology* / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D018167:Receptors, Calcitriol; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D002762:Cholecalciferol; D014212:Tretinoin