Effects of all-trans retinoic acid and interferon-gamma on expression of RAR beta gene in Tca8113 cells.
OBJECTIVE
All-trans-retinoic acid (ATRA) and interferons (IFNs) have been proven to synergistically amplify growth inhibition and apoptosis in the tongue squamous carcinoma cell line (Tca8113). Nuclear retinoic acid receptor-beta (RAR beta) was the key gene that mediated retinoid activity for squamous carcinoma cells. In order to understand the mechanism of ATRA combined with IFN gamma inhibiting growth of Tca8113 cells, this investigation focused on RAR beta mRNA expression.


METHODS
In this experiment, RT-PCR method was used to analyze the RAR beta expression level, and viable cell count assay was carried out for growth inhibition studies.


RESULTS
All-trans-retinoic acid (1 microM) and IFN gamma (1000 u/mL) inhibited cell growth by 39.2% and 44.4%, respectively. Synergistic inhibition of cell proliferation by 86.7% was found under combined treatment. The combination of suboptimal concentrations of ATRA (0.1 microM) with IFN gamma (1000 u/mL) showed a much stronger additive inhibitory effect on cell proliferation. ATRA (1 microM) and IFN gamma (1000 u/mL) increased RAR beta expression to 4 times and 3 times, respectively. The expression of RAR beta increased 12 times after treatment with combined ATRA and IFN gamma treatment.


CONCLUSIONS
These observations indicated that the use of combined ATRA and IFN may lead to enhanced antitumor effects. These results also suggested that ATRA and IFN mediated upregulating expression of RAR beta may play an important role in synergistic inhibition of proliferation in Tca8113 cells.
Chen
W T
WT
Department of Oral and Maxillofacial Surgery, Shanghai Ninth Hospital, Shanghai Second Medical University, P. R. China.
He
R G
RG
Liu
X K
XK
Zhou
X J
XJ
D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis* / Q000235:genetics; D014062:Tongue Neoplasms / Q000188:drug therapy; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D015854:Up-Regulation
D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; D014212:Tretinoin; D007371:Interferon-gamma